Trial Outcomes & Findings for Study of Efficacy and Safety of Dabrafenib in Combination With Trametinib in Pediatric Patients With BRAF V600 Mutation Positive LGG or Relapsed or Refractory HGG Tumors (NCT NCT02684058)

Last Updated: 2023-12-13

Results Overview

Percentage of participants in the LGG cohort with a best overall confirmed Complete Response (CR) or Partial Response (PR) as assessed per RANO criteria by central independent assessment. The 95% confidence intervals (CIs) were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

151 participants

Primary outcome timeframe

Up to approximately (approx.) 3 years

Results posted on

2023-12-13

Participant Flow

The study was conducted in 58 centers across 20 countries

Pediatric patients for both cohorts were screened for eligibility during the 28 days immediately prior to starting study treatment on Day 1. In the LGG cohort, 121 patients were screened of whom 110 patients were randomized in a 2:1 ratio to the dabrafenib and trametinib arm or the carboplatin with vincristine arm. 4 participants randomized to chemotherapy arm were never treated. In the HGG cohort, 46 patients were screened of whom 41 patients entered the HGG cohort

Participant milestones

Participant milestones
Measure	LGG Cohort: Dabrafenib and Trametinib Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
Treatment Period STARTED	73	37	41
Treatment Period Treated	73	33	41
Treatment Period COMPLETED	56	14	17
Treatment Period NOT COMPLETED	17	23	24
Post-treatment Efficacy Follow-up STARTED	9	22	5
Post-treatment Efficacy Follow-up COMPLETED	2	14	2
Post-treatment Efficacy Follow-up NOT COMPLETED	7	8	3
Post-treatment Survival Follow-up STARTED	11	1	9
Post-treatment Survival Follow-up COMPLETED	10	1	2
Post-treatment Survival Follow-up NOT COMPLETED	1	0	7
Crossover Treatment Period STARTED	0	12	0
Crossover Treatment Period COMPLETED	0	11	0
Crossover Treatment Period NOT COMPLETED	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	LGG Cohort: Dabrafenib and Trametinib Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
Treatment Period Progressive disease	4	10	19
Treatment Period Adverse Event	3	8	1
Treatment Period Physician Decision	5	1	2
Treatment Period New therapy for study indication	1	0	0
Treatment Period Protocol deviation	0	1	0
Treatment Period Subject/guardian decision	4	3	0
Treatment Period Death	0	0	2
Post-treatment Efficacy Follow-up Physician Decision	1	2	0
Post-treatment Efficacy Follow-up Progressive disease	4	3	0
Post-treatment Efficacy Follow-up Subject/guardian decision	2	2	0
Post-treatment Efficacy Follow-up Death	0	0	3
Post-treatment Efficacy Follow-up New therapy for study indication	0	1	0
Post-treatment Survival Follow-up Death	0	0	7
Post-treatment Survival Follow-up Lack of Efficacy	1	0	0
Crossover Treatment Period Progressive disease	0	1	0

Baseline Characteristics

Study of Efficacy and Safety of Dabrafenib in Combination With Trametinib in Pediatric Patients With BRAF V600 Mutation Positive LGG or Relapsed or Refractory HGG Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LGG Cohort: Dabrafenib and Trametinib n=73 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=37 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib n=41 Participants Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)	Total n=151 Participants Total of all reporting groups
Age, Categorical <=18 years	73 Participants n=5 Participants	37 Participants n=7 Participants	41 Participants n=5 Participants	151 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	44 Participants n=5 Participants	22 Participants n=7 Participants	23 Participants n=5 Participants	89 Participants n=4 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	15 Participants n=7 Participants	18 Participants n=5 Participants	62 Participants n=4 Participants
Race/Ethnicity, Customized White	55 Participants n=5 Participants	25 Participants n=7 Participants	25 Participants n=5 Participants	105 Participants n=4 Participants
Race/Ethnicity, Customized Asian	5 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants	19 Participants n=4 Participants
Race/Ethnicity, Customized Black Or African American	2 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	6 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	13 Participants n=4 Participants
Race/Ethnicity, Customized Other	3 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to approximately (approx.) 3 years

Population: All participants on the LGG cohort to whom study treatment had been assigned by randomization regardless of whether or not treatment was administered. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=73 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=37 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using Response Assessment in Neuro-Oncology (RANO) Criteria	46.6 Percentage of participants Interval 34.8 to 58.6	10.8 Percentage of participants Interval 3.0 to 25.4	—

PRIMARY outcome

Timeframe: Up to approx. 3.2 years

Population: All participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment.

Percentage of participants in the HGG cohort with a best overall confirmed CR or PR as assessed per RANO criteria by central independent assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=41 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
HGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria	56.1 Percentage of participants Interval 39.7 to 71.5	—	—

SECONDARY outcome

Timeframe: Up to approx. 3 years and up to approx 4.2 years

Percentage of participants in the LGG cohort with a best overall confirmed CR or PR as assessed per RANO criteria by investigator assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=73 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=37 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
LGG Cohort: ORR by Investigator Assessment Using RANO Criteria Up to approx. 3 years	54.8 Percentage of participants Interval 42.7 to 66.5	13.5 Percentage of participants Interval 4.5 to 28.8	—
LGG Cohort: ORR by Investigator Assessment Using RANO Criteria Up to approx. 4.2 years	58.9 Percentage of participants Interval 46.8 to 70.3	18.9 Percentage of participants Interval 8.0 to 35.2	—

SECONDARY outcome

Timeframe: Up to approx. 3 years and up to approx 4.2 years

Population: Participants on the LGG cohort to whom study treatment had been assigned by randomization regardless of whether or not treatment was administered with a confirmed CR or PR as per central independent review assessment using RANO criteria. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure.

Time from first documented response (PR or CR) until disease progression or death as per RANO criteria. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy, were censored at the date of the last adequate tumor evaluation. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=40 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=6 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria Up to approx. 3 years	20.3 Months Interval 12.0 to Not estimable (NA) due to the insufficient number of participants with events	NA Months Interval 6.6 to Not estimable (NA) due to the insufficient number of participants with events	—
LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria Up to approx 4.2 years	30.0 Months Interval 16.6 to Not estimable (NA) due to the insufficient number of participants with events	19.4 Months Interval 6.6 to Not estimable (NA) due to the insufficient number of participants with events	—

SECONDARY outcome

Timeframe: Up to approx. 3 years and up to approx 4.2 years

Population: Participants on the LGG cohort to whom study treatment had been assigned by randomization regardless of whether or not treatment was administered with a confirmed CR or PR as per investigator review assessment using RANO criteria. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=43 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=7 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria Up to approx. 3 years	NA Months Interval 25.5 to Not estimable (NA) due to the insufficient number of participants with events	NA Months Interval 5.3 to Not estimable (NA) due to the insufficient number of participants with events	—
LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria Up to approx 4.2 years	44.4 Months Interval 33.1 to Not estimable (NA) due to the insufficient number of participants with events	22.5 Months Interval 5.3 to Not estimable (NA) due to the insufficient number of participants with events	—

SECONDARY outcome

Timeframe: Up to approx. 3 years and up to approx 4.2 years

Population: Participants on the LGG cohort to whom study treatment had been assigned by randomization regardless of whether or not treatment was administered. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure.

Time from the date of randomization to the date of first documented disease progression as per central independent review assessment using RANO criteria or death due to any cause. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=73 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=37 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria Up to approx. 3 years	20.1 Months Interval 12.8 to Not estimable (NA) due to the insufficient number of participants with events	7.4 Months Interval 3.6 to 11.8	—
LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria Up to approx 4.2 years	24.9 Months Interval 12.9 to 31.6	7.2 Months Interval 2.8 to 11.2	—

SECONDARY outcome

Timeframe: Up to approx. 3 years and up to approx 4.2 years

Time from the date of randomization to the date of first documented disease progression as per investigator assessment using RANO criteria or death due to any cause. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=73 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=37 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Investigator Assessment Using RANO Criteria Up to approx. 3 years	NA Months Not estimable (NA) due to the insufficient number of participants with events	NA Months Interval 12.6 to Not estimable (NA) due to the insufficient number of participants with events	—
LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Investigator Assessment Using RANO Criteria Up to approx 4.2 years	46.0 Months Interval 38.6 to Not estimable (NA) due to the insufficient number of participants with events	30.8 Months Interval 7.0 to Not estimable (NA) due to the insufficient number of participants with events	—

SECONDARY outcome

Timeframe: Up to approx. 4.2 years

Time from randomization to first documented response of CR or PR as per central independent assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients without an event were censored either at the maximum follow-up time (if they experienced disease progression or death), or at their last tumor assessment date. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=73 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=37 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
LGG Cohort: Kaplan-Meier Estimates of Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria	11.0 Months Interval 6.0 to Not estimable (NA) due to the insufficient number of participants with events	NA Months Not estimable (NA) due to the insufficient number of participants with events	—

SECONDARY outcome

Timeframe: Up to approx. 4.2 years

Time from randomization to first documented response of CR or PR as per investigator assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients without an event were censored either at the maximum follow-up time (if they experienced disease progression or death), or at their last tumor assessment date. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=73 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=37 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
LGG Cohort: Kaplan-Meier Estimates of Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria	7.4 Months Interval 5.3 to Not estimable (NA) due to the insufficient number of participants with events	NA Months Not estimable (NA) due to the insufficient number of participants with events	—

SECONDARY outcome

Timeframe: Up to approx. 4.2 years

Percentage of participants with a best overall response of CR or PR, or stable disease (SD) which lasts for 24 weeks or longer. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. SD: Partient did not qualify for CR, PR, or progressive disease and has stable nonenhancing (T2/FLAIR) lesions on same or lower doses of corticosteroids compared with baseline scan and clinically stable status.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=73 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=37 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
LGG Cohort: Clinical Benefit Rate (CBR) by Central Independent Assessment Using RANO Criteria	86.3 Percentage of participants Interval 76.2 to 93.2	43.2 Percentage of participants Interval 27.1 to 60.5	—

SECONDARY outcome

Timeframe: Up to approx. 4.2 years

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=73 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=37 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
LGG Cohort: Clinical Benefit Rate (CBR) by Investigator Assessment Using RANO Criteria	91.8 Percentage of participants Interval 83.0 to 96.9	56.8 Percentage of participants Interval 39.5 to 72.9	—

SECONDARY outcome

Timeframe: Up to 4.6 years

Time from first dose to death due to any cause in the LGG cohort. Confidence Intervals were estimated using the Brookmeyer Crowley method. If a patient was not known to have died at the time of analysis cut-off, OS was censored at the date of last contact.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=73 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=37 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
LGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS)	NA Months Not estimable (NA) due to the insufficient number of participants with events	NA Months Not estimable (NA) due to the insufficient number of participants with events	—

SECONDARY outcome

Timeframe: 2 years from first dose

OS was defined as the time from the first dose to death due to any cause in the LGG cohort. The 2-year Kaplan-Meier OS estimate represented the estimated percentage of participants remaining free from OS events for up to 2 years. If a patient was not known to have died at the time of analysis cut-off, OS was censored at the date of last contact

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=73 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=37 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
LGG Cohort: 2-year OS Estimate	100.0 Percentage of participants Interval 100.0 to 100.0	96.9 Percentage of participants Interval 79.8 to 99.6	—

SECONDARY outcome

Timeframe: Up to approx. 3.2 years and up to approx. 4.8 years

Population: All participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment.

ORR in the HGG cohort defined as the percentage of participants in the HGG cohort with a best overall confirmed CR or PR as assessed per RANO criteria by investigator assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=41 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
HGG Cohort: ORR by Investigator Assessment Using RANO Criteria Up to approx. 3.2 years	58.5 Percentage of participants Interval 42.1 to 73.7	—	—
HGG Cohort: ORR by Investigator Assessment Using RANO Criteria Up to approx. 4.8 years	61.0 Percentage of participants Interval 44.5 to 75.8	—	—

SECONDARY outcome

Timeframe: Up to approx. 3.2 years and up to approx. 4.8 years

Population: Participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment with a confirmed CR or PR as per central independent assessment using RANO criteria

Time from first documented response (PR or CR) until disease progression or death as per central independent assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=23 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria Up to approx. 3.2 years	22.2 Months Interval 7.6 to Not estimable (NA) due to the insufficient number of participants with events	—	—
HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria Up to approx. 4.8 years	27.4 Months Interval 9.2 to Not estimable (NA) due to the insufficient number of participants with events	—	—

SECONDARY outcome

Timeframe: Up to approx. 3.2 years and up to approx. 4.8 years

Population: Participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment with a confirmed CR or PR as per investigator assessment using RANO criteria

Time from first documented response (PR or CR) until disease progression or death as per investigator assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=25 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria Up to approx. 3.2 years	26.6 Months Interval 14.9 to Not estimable (NA) due to the insufficient number of participants with events	—	—
HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria Up to approx. 4.8 years	32.7 Months Interval 14.9 to Not estimable (NA) due to the insufficient number of participants with events	—	—

SECONDARY outcome

Timeframe: Up to approx. 4.8 years

Population: All participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment.

Time from the date of first dose of study treatment to the date of first documented disease progression as per central independent review assessment using RANO criteria or death due to any cause. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=41 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
HGG Cohort: Kaplan-Meier Estimates of Progression Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria	9.0 Months Interval 5.3 to 20.1	—	—

SECONDARY outcome

Timeframe: Up to approx. 4.8 years

Population: All participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment.

Time from the date of first dose of study treatment to the date of first documented disease progression as per investigator assessment using RANO criteria or death due to any cause. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=41 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
HGG Cohort: Kaplan-Meier Estimates of Progression Free Survival (PFS) as Per Investigatort Assessment Using RANO Criteria	24.0 Months Interval 12.5 to Not estimable (NA) due to the insufficient number of participants with events	—	—

SECONDARY outcome

Timeframe: Up to approx. 4.8 years

Population: All participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment.

Time from start of treatment to first documented response of CR or PR as per independent assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients without an event were censored either at the maximum follow-up time (if they experienced disease progression or death), or at their last tumor assessment date. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=41 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
HGG Cohort: Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria	8.5 Months Interval 2.0 to Not estimable (NA) due to the insufficient number of participants with events	—	—

SECONDARY outcome

Timeframe: Up to approx. 4.8 years

Population: All participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment.

Time from start of treatment to first documented response of CR or PR as per investigator assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients without an event were censored either at the maximum follow-up time (if they experienced disease progression or death), or at their last tumor assessment date. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=41 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
HGG Cohort: Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria	3.4 Months Interval 1.8 to Not estimable (NA) due to the insufficient number of participants with events	—	—

SECONDARY outcome

Timeframe: Up to approx. 4.8 years

Population: All participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=41 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
HGG Cohort: Clinical Benefit Rate (CBR) as Per Central Independent Assessment Using RANO Criteria	65.9 Percentage of participants Interval 49.4 to 79.9	—	—

SECONDARY outcome

Timeframe: Up to approx. 4.8 years

Population: All participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=41 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
HGG Cohort: Clinical Benefit Rate (CBR) as Per Investigator Assessment Using RANO Criteria	75.6 Percentage of participants Interval 59.7 to 87.6	—	—

SECONDARY outcome

Timeframe: Up to 5.1 years

Population: All participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=41 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
HGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS)	NA Months Interval 19.8 to Not estimable (NA) due to the insufficient number of participants with events	—	—

SECONDARY outcome

Timeframe: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Population: Participants who received at least one dose of trametinib with an evaluable AUClast PK parameter

Pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast).

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=36 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=55 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
AUClast for Trametinib	282 hour (hr) * nanogram (ng)/mililiter (mL) Geometric Coefficient of Variation 53.7	328 hour (hr) * nanogram (ng)/mililiter (mL) Geometric Coefficient of Variation 33.4	—

SECONDARY outcome

Timeframe: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Population: Participants who received at least one dose of trametinib with an evaluable Cmax PK parameter

PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum plasma drug concentration after single dose administration

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=36 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=55 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
Cmax for Trametinib	21.3 ng/mL Geometric Coefficient of Variation 36.3	22.7 ng/mL Geometric Coefficient of Variation 41.1	—

SECONDARY outcome

Timeframe: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Population: Participants who received at least one dose of trametinib with an evaluable AUCtau PK parameter

PK parameters were calculated by standard non-compartmental analysis. AUCtau is the AUC calculated to the end of a dosing interval (tau) at steady-state

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=33 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=44 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
AUCtau for Trametinib	307 hr * ng/mL Geometric Coefficient of Variation 22.8	339 hr * ng/mL Geometric Coefficient of Variation 22.2	—

SECONDARY outcome

Timeframe: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Population: Participants who received at least one dose of trametinib with an evaluable Tmax PK parameter

PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum plasma concentration. Actual recorded sampling times were considered for the calculations.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=36 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=55 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
Tmax for Trametinib	1.67 hour Geometric Coefficient of Variation 58.1	1.53 hour Geometric Coefficient of Variation 54.6	—

SECONDARY outcome

Timeframe: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Population: Participants who received at least one dose of trametinib with an evaluable T1/2 PK parameter

PK parameters were calculated by standard non-compartmental analysis. T1/2 is the elimination half-life

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=24 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=14 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
T1/2 for Trametinib	26.7 hour Geometric Coefficient of Variation 62.6	25.7 hour Geometric Coefficient of Variation 37.9	—

SECONDARY outcome

Timeframe: Week 3 Day 1 pre-dose

Population: Participants who received at least one dose of trametinib with an evaluable Ctrough PK parameter

PK parameters were calculated by standard non-compartmental analysis. Ctrough is the pre-dose plasma concentration

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=36 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=55 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
Ctrough for Trametinib	8.73 ng/ml Geometric Coefficient of Variation 72.7	9.82 ng/ml Geometric Coefficient of Variation 30.1	—

SECONDARY outcome

Timeframe: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Population: Participants who received at least one dose of dabrafenib with an evaluable AUClast PK parameter

PK parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast).

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=34 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=54 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
AUClast for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Dabrafenib	4330 hr * ng/ml Geometric Coefficient of Variation 44.7	4870 hr * ng/ml Geometric Coefficient of Variation 60.3	—
AUClast for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Carboxy-dabrafenib	73400 hr * ng/ml Geometric Coefficient of Variation 31.5	64200 hr * ng/ml Geometric Coefficient of Variation 46.9	—
AUClast for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Desmethyl-dabrafenib	3520 hr * ng/ml Geometric Coefficient of Variation 60.2	3870 hr * ng/ml Geometric Coefficient of Variation 68.2	—
AUClast for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Hydroxy-dabrafenib	2810 hr * ng/ml Geometric Coefficient of Variation 36.5	2980 hr * ng/ml Geometric Coefficient of Variation 50.1	—

SECONDARY outcome

Timeframe: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Population: Participants who received at least one dose of dabrafenib with an evaluable Cmax PK parameter

PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum plasma drug concentration after single dose administration

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=34 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=54 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
Cmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Dabrafenib	1520 ng/ml Geometric Coefficient of Variation 65.9	1330 ng/ml Geometric Coefficient of Variation 93.5	—
Cmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Carboxy-dabrafenib	9050 ng/ml Geometric Coefficient of Variation 31.4	7210 ng/ml Geometric Coefficient of Variation 51.6	—
Cmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Desmethyl-dabrafenib	388 ng/ml Geometric Coefficient of Variation 67.2	377 ng/ml Geometric Coefficient of Variation 67.2	—
Cmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Hydroxy-dabrafenib	801 ng/ml Geometric Coefficient of Variation 58.8	687 ng/ml Geometric Coefficient of Variation 82.6	—

SECONDARY outcome

Timeframe: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Population: Participants who received at least one dose of dabrafenib with an evaluable AUCtau PK parameter

PK parameters were calculated by standard non-compartmental analysis. AUCtau is the AUC calculated to the end of a dosing interval (tau) at steady-state

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=34 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=47 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
AUCtau for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Dabrafenib	4300 hr * ng/ml Geometric Coefficient of Variation 44.7	4910 hr * ng/ml Geometric Coefficient of Variation 54.0	—
AUCtau for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Carboxy-dabrafenib	71200 hr * ng/ml Geometric Coefficient of Variation 34.0	60700 hr * ng/ml Geometric Coefficient of Variation 45.7	—
AUCtau for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Desmethyl-dabrafenib	3360 hr * ng/ml Geometric Coefficient of Variation 57.7	3660 hr * ng/ml Geometric Coefficient of Variation 66.9	—
AUCtau for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Hydroxy-dabrafenib	2840 hr * ng/ml Geometric Coefficient of Variation 35.7	2960 hr * ng/ml Geometric Coefficient of Variation 47.4	—

SECONDARY outcome

Timeframe: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Population: Participants who received at least one dose of dabrafenib with an evaluable Tmax PK parameter

PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum plasma concentration. Actual recorded sampling times were considered for the calculations.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=34 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=54 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
Tmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Dabrafenib	1.47 hr Geometric Coefficient of Variation 54.2	1.47 hr Geometric Coefficient of Variation 52.9	—
Tmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Carboxy-dabrafenib	3.37 hr Geometric Coefficient of Variation 35.4	3.66 hr Geometric Coefficient of Variation 51.4	—
Tmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Desmethyl-dabrafenib	2.21 hr Geometric Coefficient of Variation 76.7	2.29 hr Geometric Coefficient of Variation 82.0	—
Tmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Hydroxy-dabrafenib	1.97 hr Geometric Coefficient of Variation 45.9	1.68 hr Geometric Coefficient of Variation 57.8	—

SECONDARY outcome

Timeframe: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Population: Participants who received at least one dose of dabrafenib with an evaluable T1/2 PK parameter

PK parameters were calculated by standard non-compartmental analysis. T1/2 is the elimination half-life

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=33 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=18 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
T1/2 for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Dabrafenib	2.48 hr Geometric Coefficient of Variation 36.6	3.09 hr Geometric Coefficient of Variation 36.4	—
T1/2 for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Carboxy-dabrafenib	7.12 hr Geometric Coefficient of Variation 32.3	6.59 hr Geometric Coefficient of Variation 43.9	—
T1/2 for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Desmethyl-dabrafenib	7.06 hr Geometric Coefficient of Variation 392.5	16.1 hr	—
T1/2 for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Hydroxy-dabrafenib	2.66 hr Geometric Coefficient of Variation 47.8	3.52 hr Geometric Coefficient of Variation 71.7	—

SECONDARY outcome

Timeframe: Week 3 Day 1 pre-dose

Population: Participants who received at least one dose of dabrafenib with an evaluable Ctrough PK parameter

PK parameters were calculated by standard non-compartmental analysis. Ctrough is the pre-dose plasma concentration

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=34 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=54 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
Ctrough for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Dabrafenib	38.0 ng/ml Geometric Coefficient of Variation 162.0	46.0 ng/ml Geometric Coefficient of Variation 125.1	—
Ctrough for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Carboxy-dabrafenib	3980 ng/ml Geometric Coefficient of Variation 46.1	3190 ng/ml Geometric Coefficient of Variation 54.4	—
Ctrough for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Desmethyl-dabrafenib	275 ng/ml Geometric Coefficient of Variation 116.5	310 ng/ml Geometric Coefficient of Variation 70.1	—
Ctrough for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) Hydroxy-dabrafenib	41.8 ng/ml Geometric Coefficient of Variation 123.8	44.3 ng/ml Geometric Coefficient of Variation 99.7	—

SECONDARY outcome

Timeframe: Week 1 and Week 5

Population: Participants who received at least one dose of dabrafenib as dispersible tablet for oral suspension and completed the palatability questionnaire for dabrafenib at week 1 or 5.

Participants who received the dabrafenib dispersible tablets for oral suspension completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on how it tasted before rinsing with water, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=8 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=32 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth Week 1 · Very good, good, and neither good nor bad	5 Participants	18 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth Week 1 · Bad	2 Participants	4 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth Week 1 · Very bad	0 Participants	0 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth Week 1 · Unable to answer question	0 Participants	5 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth Week 1 · Missing	1 Participants	5 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth Week 5 · Very good, good, and neither good nor bad	6 Participants	20 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth Week 5 · Bad	0 Participants	1 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth Week 5 · Very bad	0 Participants	1 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth Week 5 · Unable to answer question	0 Participants	2 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth Week 5 · Missing	2 Participants	8 Participants	—

SECONDARY outcome

Timeframe: Week 1 and Week 5

Population: Participants who received at least one dose of trametinib oral solution and completed the palatability questionnaire for trametinib at week 1 or 5.

Participants who received the trametinib oral solution completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on how it tasted before rinsing with water, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=8 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=35 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth Week 1 · Very good, good, and neither good nor bad	2 Participants	15 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth Week 1 · Bad	3 Participants	5 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth Week 1 · Very bad	0 Participants	2 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth Week 1 · Unable to answer question	1 Participants	4 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth Week 1 · Missing	2 Participants	9 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth Week 5 · Very good, good, and neither good nor bad	5 Participants	12 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth Week 5 · Bad	0 Participants	6 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth Week 5 · Very bad	0 Participants	2 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth Week 5 · Unable to answer question	0 Participants	1 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth Week 5 · Missing	3 Participants	14 Participants	—

SECONDARY outcome

Timeframe: Week 1 and Week 5

Population: Participants who received at least one dose of dabrafenib as dispersible tablet for oral suspension and completed the palatability questionnaire for dabrafenib at week 1 or 5.

Participants who received the dabrafenib dispersible tablets for oral suspension completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the after-taste of the medication after the medication was swallowed, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=8 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=32 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed Week 1 · Very good, good, and neither good nor bad	4 Participants	13 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed Week 1 · Bad	1 Participants	6 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed Week 1 · Very bad	0 Participants	0 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed Week 1 · Unable to answer question	0 Participants	3 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed Week 1 · Missing	3 Participants	10 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed Week 5 · Very good, good, and neither good nor bad	5 Participants	16 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed Week 5 · Bad	0 Participants	2 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed Week 5 · Very bad	0 Participants	0 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed Week 5 · Unable to answer question	0 Participants	3 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed Week 5 · Missing	3 Participants	11 Participants	—

SECONDARY outcome

Timeframe: Week 1 and Week 5

Population: Participants who received at least one dose of trametinib oral solution and completed the palatability questionnaire for trametinib at week 1 or 5.

Participants who received the trametinib oral solution completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the after-taste of the medication after the medication was swallowed, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=8 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=35 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed Week 1 · Very good, good, and neither good nor bad	3 Participants	15 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed Week 1 · Bad	3 Participants	5 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed Week 1 · Very bad	0 Participants	2 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed Week 1 · Unable to answer question	0 Participants	2 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed Week 1 · Missing	2 Participants	11 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed Week 5 · Very good, good, and neither good nor bad	5 Participants	16 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed Week 5 · Bad	0 Participants	3 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed Week 5 · Very bad	0 Participants	1 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed Week 5 · Unable to answer question	0 Participants	2 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed Week 5 · Missing	3 Participants	13 Participants	—

SECONDARY outcome

Timeframe: Week 1 and Week 5

Population: Participants who received at least one dose of dabrafenib as dispersible tablet for oral suspension and completed the palatability questionnaire for dabrafenib at week 1 or 5.

Participants who received the dabrafenib dispersible tablets for oral suspension completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the immediate reaction once the medication was placed into their mouth, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=8 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=32 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth Week 1 · Very good, good, and neither good nor bad	4 Participants	13 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth Week 1 · Bad	1 Participants	5 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth Week 1 · Very bad	0 Participants	1 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth Week 1 · Unable to answer question	0 Participants	3 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth Week 1 · Missing	3 Participants	10 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth Week 5 · Very good, good, and neither good nor bad	5 Participants	18 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth Week 5 · Bad	0 Participants	1 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth Week 5 · Very bad	0 Participants	0 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth Week 5 · Unable to answer question	0 Participants	2 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth Week 5 · Missing	3 Participants	11 Participants	—

SECONDARY outcome

Timeframe: Week 1 and Week 5

Population: Participants who received at least one dose of trametinib oral solution and completed the palatability questionnaire for trametinib at week 1 or 5.

Participants who received the trametinib oral solution completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the immediate reaction once the medication was placed into their mouth, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=8 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=35 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth Week 1 · Very good, good, and neither good nor bad	3 Participants	15 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth Week 1 · Bad	3 Participants	4 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth Week 1 · Very Bad	0 Participants	3 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth Week 1 · Unable to answer question	0 Participants	2 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth Week 1 · Missing	2 Participants	11 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth Week 5 · Very good, good, and neither good nor bad	5 Participants	15 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth Week 5 · Bad	0 Participants	4 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth Week 5 · Very Bad	0 Participants	2 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth Week 5 · Unable to answer question	0 Participants	1 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth Week 5 · Missing	3 Participants	13 Participants	—

SECONDARY outcome

Timeframe: Week 1 and Week 5

Population: Participants who received at least one dose of dabrafenib as dispersible tablet for oral suspension and completed the palatability questionnaire for dabrafenib at week 1 or 5.

Participants who received the dabrafenib dispersible tablets for oral suspension completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the after-taste of the medication after rinsing with water, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=8 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=32 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water Week 1 · Very bad	0 Participants	0 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water Week 1 · Unable to answer question	1 Participants	7 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water Week 1 · Bad	2 Participants	5 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water Week 1 · Very good, good, and neither good nor bad	4 Participants	15 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water Week 1 · Missing	1 Participants	5 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water Week 5 · Very good, good, and neither good nor bad	6 Participants	17 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water Week 5 · Bad	0 Participants	2 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water Week 5 · Very bad	0 Participants	1 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water Week 5 · Unable to answer question	0 Participants	4 Participants	—
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water Week 5 · Missing	2 Participants	8 Participants	—

SECONDARY outcome

Timeframe: Week 1 and Week 5

Population: Participants who received at least one dose of trametinib oral solution and completed the palatability questionnaire for trametinib at week 1 or 5.

Participants who received the trametinib oral solution completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the after-taste of the medication after rinsing with water, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=8 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=35 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water Week 1 · Very good, good, and neither good nor bad	2 Participants	15 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water Week 1 · Bad	2 Participants	3 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water Week 1 · Very Bad	0 Participants	2 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water Week 1 · Unable to answer question	2 Participants	6 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water Week 1 · Missing	2 Participants	9 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water Week 5 · Very good, good, and neither good nor bad	4 Participants	14 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water Week 5 · Bad	0 Participants	2 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water Week 5 · Very Bad	0 Participants	2 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water Week 5 · Unable to answer question	1 Participants	3 Participants	—
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water Week 5 · Missing	3 Participants	14 Participants	—

SECONDARY outcome

Timeframe: Baseline, and Day 1 of Week 5, 8, 16, 24, 32, 49, 48 and 56, and thereafter every 16 weeks until end of treatment (EOT), EOT, and every 16 weeks in the post-treatment efficacy follow-up phase until disease progression (assessed up to 4.6 years)

Population: All participants on the LGG cohort to whom study treatment had been assigned by randomization (regardless of whether or not treatment was administered) and contributed to this analysis. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure. Number analyzed indicated number of participants with available data for this outcome measure at the specified timepoints.

The PROMIS Parent Proxy Global Health 7+2 was used to evaluate the quality of life of participants. The questionnaire included 7 items measuring the global health of the patient. 4 items used a 5-level Likert scale with 1=poor and 5=excellent; 1 item used a 5-level Likert scale with 1=never and 5=always; and 2 items used a 5-level Likert scale with 1=never and 5=almost always. The total raw global health score, ranging from 7 to 35, was computed by summing item values, with higher scores indicating better overall well-being. Raw scores were then transformed into T-scores, standardized with a mean of 50 and a standard deviation of 10. Higher T-scores reflected better global health status. Participants who discontinued treatment for reasons other than disease progression entered the post-treatment efficacy follow-up phase, where the questionnaire was performed every 16 weeks until disease progression, withdrawal of consent by patient or a parental/legal guardian, or lost to follow-up.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=61 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=23 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Baseline	42.67 Score on a Scale Standard Deviation 10.068	42.89 Score on a Scale Standard Deviation 10.502	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Week 5 Day 1	42.14 Score on a Scale Standard Deviation 9.439	39.06 Score on a Scale Standard Deviation 10.109	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Week 8 Day 1	43.83 Score on a Scale Standard Deviation 9.461	38.36 Score on a Scale Standard Deviation 7.759	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Week 16 Day 1	44.68 Score on a Scale Standard Deviation 9.159	41.11 Score on a Scale Standard Deviation 10.798	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Week 24 Day 1	45.27 Score on a Scale Standard Deviation 9.168	36.57 Score on a Scale Standard Deviation 6.241	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Week 32 Day 1	45.46 Score on a Scale Standard Deviation 8.887	40.96 Score on a Scale Standard Deviation 7.159	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Week 40 Day 1	45.37 Score on a Scale Standard Deviation 9.687	38.84 Score on a Scale Standard Deviation 4.960	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Week 48 Day 1	44.83 Score on a Scale Standard Deviation 9.421	41.56 Score on a Scale Standard Deviation 6.953	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Week 56 Day 1	44.54 Score on a Scale Standard Deviation 8.876	38.66 Score on a Scale Standard Deviation 8.851	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Week 72 Day 1	44.21 Score on a Scale Standard Deviation 8.967	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Week 88 Day 1	44.91 Score on a Scale Standard Deviation 8.847	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Week 104 Day 1	45.60 Score on a Scale Standard Deviation 8.231	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Week 120 Day 1	44.41 Score on a Scale Standard Deviation 7.317	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Week 136 Day 1	44.45 Score on a Scale Standard Deviation 8.074	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Week 152 Day 1	47.88 Score on a Scale Standard Deviation 10.534	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Week 168 Day 1	46.48 Score on a Scale Standard Deviation 9.888	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score EOT	44.98 Score on a Scale Standard Deviation 10.274	39.69 Score on a Scale Standard Deviation 10.536	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Post Treatment Follow-Up 1	45.40 Score on a Scale	45.53 Score on a Scale Standard Deviation 6.288	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Post Treatment Follow-Up 2	27.70 Score on a Scale	39.70 Score on a Scale	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Post Treatment Follow-Up 3	43.60 Score on a Scale	34.60 Score on a Scale	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Post Treatment Follow-Up 4	31.20 Score on a Scale	43.60 Score on a Scale Standard Deviation 8.061	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Post Treatment Follow-Up 5	29.40 Score on a Scale	37.90 Score on a Scale	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Post Treatment Follow-Up 6	—	36.45 Score on a Scale Standard Deviation 7.425	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score Post Treatment Follow-Up 8	—	37.90 Score on a Scale	—

SECONDARY outcome

The PROMIS Parent Proxy Global Health 7+2 was used to evaluate the quality of life of participants. The questionnaire included 1 item measuring the pain of the participants. Pain item used a 5-level Likert scale with 1= never and 5= almost always, higher scores indicate worsening pain. Raw scores were then converted into T-scores, standardized with a mean of 50 and a standard deviation of 10. Higher T-scores indicated more severe pain experiences. Participants who discontinued treatment for reasons other than disease progression entered the post-treatment efficacy follow-up phase, where the PROMIS Parent Proxy Global 7+2 Health questionnaire was performed every 16 weeks until disease progression, withdrawal of consent by patient or a parental/legal guardian, or lost to follow-up.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=61 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=23 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Baseline	52.14 Score on a Scale Standard Deviation 7.658	52.64 Score on a Scale Standard Deviation 7.054	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Week 5 Day 1	50.11 Score on a Scale Standard Deviation 7.275	50.97 Score on a Scale Standard Deviation 6.263	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Week 8 Day 1	49.93 Score on a Scale Standard Deviation 7.727	51.00 Score on a Scale Standard Deviation 6.037	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Week 16 Day 1	49.72 Score on a Scale Standard Deviation 7.300	51.75 Score on a Scale Standard Deviation 6.330	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Week 24 Day 1	50.65 Score on a Scale Standard Deviation 7.450	51.81 Score on a Scale Standard Deviation 7.937	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Week 32 Day 1	48.77 Score on a Scale Standard Deviation 6.647	49.59 Score on a Scale Standard Deviation 6.387	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Week 40 Day 1	49.87 Score on a Scale Standard Deviation 6.389	52.52 Score on a Scale Standard Deviation 7.402	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Week 48 Day 1	49.89 Score on a Scale Standard Deviation 6.581	51.20 Score on a Scale Standard Deviation 5.903	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Week 56 Day 1	48.14 Score on a Scale Standard Deviation 6.496	53.99 Score on a Scale Standard Deviation 5.466	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Week 72 Day 1	49.46 Score on a Scale Standard Deviation 6.498	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Week 88 Day 1	47.82 Score on a Scale Standard Deviation 6.083	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Week 104 Day 1	48.74 Score on a Scale Standard Deviation 6.605	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Week 120 Day 1	48.56 Score on a Scale Standard Deviation 7.583	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Week 136 Day 1	46.16 Score on a Scale Standard Deviation 5.305	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Week 152 Day 1	47.42 Score on a Scale Standard Deviation 6.765	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Week 168 Day 1	48.61 Score on a Scale Standard Deviation 6.298	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score EOT	51.46 Score on a Scale Standard Deviation 6.830	52.87 Score on a Scale Standard Deviation 6.113	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Post Treatment Follow-Up 1	53.05 Score on a Scale	50.60 Score on a Scale Standard Deviation 4.900	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Post Treatment Follow-Up 2	58.51 Score on a Scale	43.25 Score on a Scale	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Post Treatment Follow-Up 3	53.05 Score on a Scale	43.25 Score on a Scale	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Post Treatment Follow-Up 4	58.51 Score on a Scale	43.25 Score on a Scale Standard Deviation 0.000	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Post Treatment Follow-Up 5	58.51 Score on a Scale	43.25 Score on a Scale	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Post Treatment Follow-Up 6	—	50.88 Score on a Scale Standard Deviation 10.790	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score Post Treatment Follow-Up 8	—	43.25 Score on a Scale	—

SECONDARY outcome

Population: All participants on the LGG cohort to whom study treatment had been assigned by randomization regardless of whether or not treatment was administered and contributed to this analysis. According to the intent to treat principle, patients were analyzed according to the treatment they had been assigned to during the randomization procedure. Number analyzed indicated number of participants with available data for this outcome measure at the specified timepoints.

The PROMIS Parent Proxy Global Health 7+2 was used to evaluate the quality of life of participants. The questionnaire included 1 item measuring the fatigue interference of the participants. Fatigue item used a 5-level Likert scale with 1= never and 5= almost always, higher scores indicate worsening fatigue. Raw scores were then converted into T-scores, standardized with a mean of 50 and a standard deviation of 10. Higher T-scores indicated a greater level of reported fatigue. Participants who discontinued treatment for reasons other than disease progression entered the post-treatment efficacy follow-up phase, where the PROMIS Parent Proxy Global 7+2 Health questionnaire was performed every 16 weeks until disease progression, withdrawal of consent by patient or a parental/legal guardian, or lost to follow-up.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=61 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=23 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Baseline	53.30 Score on a Scale Standard Deviation 6.731	54.37 Score on a Scale Standard Deviation 7.981	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Week 5 Day 1	53.96 Score on a Scale Standard Deviation 7.588	56.88 Score on a Scale Standard Deviation 6.430	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Week 8 Day 1	52.68 Score on a Scale Standard Deviation 6.967	58.10 Score on a Scale Standard Deviation 4.823	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Week 16 Day 1	51.22 Score on a Scale Standard Deviation 6.983	57.81 Score on a Scale Standard Deviation 6.193	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Week 24 Day 1	51.04 Score on a Scale Standard Deviation 8.005	55.02 Score on a Scale Standard Deviation 7.248	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Week 32 Day 1	52.49 Score on a Scale Standard Deviation 7.219	57.66 Score on a Scale Standard Deviation 5.899	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Week 40 Day 1	52.27 Score on a Scale Standard Deviation 7.450	58.49 Score on a Scale Standard Deviation 7.072	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Week 48 Day 1	51.65 Score on a Scale Standard Deviation 7.362	53.48 Score on a Scale Standard Deviation 8.004	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Week 56 Day 1	50.51 Score on a Scale Standard Deviation 7.150	57.63 Score on a Scale Standard Deviation 7.254	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Week 72 Day 1	49.93 Score on a Scale Standard Deviation 6.910	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Week 88 Day 1	50.52 Score on a Scale Standard Deviation 7.358	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Week 104 Day 1	51.11 Score on a Scale Standard Deviation 6.899	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Week 120 Day 1	50.40 Score on a Scale Standard Deviation 7.317	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Week 136 Day 1	50.97 Score on a Scale Standard Deviation 8.667	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Week 152 Day 1	47.71 Score on a Scale Standard Deviation 8.037	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Week 168 Day 1	48.21 Score on a Scale Standard Deviation 8.188	—	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score EOT	52.35 Score on a Scale Standard Deviation 7.565	56.88 Score on a Scale Standard Deviation 5.246	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Post Treatment Follow-Up 1	48.94 Score on a Scale	52.36 Score on a Scale Standard Deviation 6.840	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Post Treatment Follow-Up 2	62.62 Score on a Scale	62.62 Score on a Scale	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Post Treatment Follow-Up 3	48.94 Score on a Scale	48.94 Score on a Scale	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Post Treatment Follow-Up 4	56.07 Score on a Scale	48.94 Score on a Scale Standard Deviation 0.000	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Post Treatment Follow-Up 5	62.62 Score on a Scale	48.94 Score on a Scale	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Post Treatment Follow-Up 6	—	55.78 Score on a Scale Standard Deviation 9.673	—
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score Post Treatment Follow-Up 8	—	48.94 Score on a Scale	—

POST_HOC outcome

Timeframe: On-treatment: Up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment: Up to 4.6 years (LGG) and 5.1 years (HGG).Crossover arm: on-treatment: up to 4.2 years

Population: Safety set including all participants who received at least one dose of study treatment

On-treatment deaths were collected from 1st dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment (efficacy/survival) follow-up deaths were collected from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG). For participants in the LGG cohort who crossed over to dabrafenib and trametinib, on-treatment deaths were collected from 1st dose to 30 days after last dose of crossover treatment, up to 4.2 years. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=73 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=33 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib n=41 Participants Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
All-collected Deaths On- treatment deaths	0 Participants	0 Participants	6 Participants
All-collected Deaths Post-treatment efficacy/survival follow-up deaths	0 Participants	0 Participants	11 Participants
All-collected Deaths Crossover on-treatment deaths	—	1 Participants	—
All-collected Deaths Crossover post-treatment efficacy/survival follow-up deaths	0 Participants	0 Participants	0 Participants
All-collected Deaths All deaths	0 Participants	1 Participants	17 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to approx 4.2 years

Percentage of participants with a best overall confirmed CR or PR as assessed per RANO criteria by central independent assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. This analysis was conducted at the end of the trial (after the primary endpoint analysis cut-off date) and includes a longer follow-up time

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=73 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine n=37 Participants Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria (Longer Follow-up Time)	54.8 Percentage of participants Interval 42.7 to 66.5	16.2 Percentage of participants Interval 6.2 to 32.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to approx 4.8 years

Population: All participants on the HGG cohort to whom study treatment had been assigned and who received at least one dose of study treatment

Outcome measures

Outcome measures
Measure	LGG Cohort: Dabrafenib and Trametinib n=41 Participants Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)	LGG Cohort: Carboplatin and Vincristine Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Participants were allowed to crossover to dabrafenib and trametinib after centrally confirmed and RANO-defined disease progression.	HGG Cohort: Dabrafenib and Trametinib Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)
HGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria (Longer Follow-up Time)	56.1 Percentage of participants Interval 39.7 to 71.5	—	—

Adverse Events

HGG Cohort: Dabrafenib and Trametinib (On-treatment)

Serious events: 28 serious events

Other events: 41 other events

Deaths: 6 deaths

HGG Cohort: Dabrafenib and Trametinib (Post-treatment Follow-up)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 11 deaths

LGG Cohort: Dabrafenib and Trametinib (On-treatment)

Serious events: 34 serious events

Other events: 73 other events

Deaths: 0 deaths

LGG Cohort: Dabrafenib and Trametinib (Post-treatment Follow-up)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

LGG Cohort: Carboplatin and Vincristine (On-treatment)

Serious events: 14 serious events

Other events: 33 other events

Deaths: 0 deaths

LGG Cohort: Carboplatin and Vincristine (Post-treatment Follow-up)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

LGG Cohort: Carboplatin and Vincristine (Crossover On-treatment)

Serious events: 4 serious events

Other events: 11 other events

Deaths: 1 deaths

LGG Cohort: Carboplatin and Vincristine (Crossover Post-treatment Follow-up)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	HGG Cohort: Dabrafenib and Trametinib (On-treatment) n=41 participants at risk AEs collected during on-treatment period with dabrafenib and trametinib in the HGG cohort (up to 30 days post- treatment)	HGG Cohort: Dabrafenib and Trametinib (Post-treatment Follow-up) Deaths collected in the post- treatment follow-up period for participants in the HGG cohort treated with dabrafenib and trametinib (starting from day 31 post- treatment). No AEs were collected during this period	LGG Cohort: Dabrafenib and Trametinib (On-treatment) n=73 participants at risk AEs collected during on-treatment period with dabrafenib and trametinib in the LGG cohort (up to 30 days post- treatment)	LGG Cohort: Dabrafenib and Trametinib (Post-treatment Follow-up) Deaths collected in the post- treatment follow-up period for participants in the LGG cohort treated with dabrafenib and trametinib (starting from day 31 post- treatment). No AEs were collected during this period	LGG Cohort: Carboplatin and Vincristine (On-treatment) n=33 participants at risk AEs collected during on-treatment period with carboplatin and vincristine in the LGG cohort (up to 30 days post- treatment or start date of crossover treatment, whichever was earlier)	LGG Cohort: Carboplatin and Vincristine (Post-treatment Follow-up) Deaths collected in the post- treatment follow-up period (starting from day 31 post- treatment) for participants in the LGG cohort treated with carboplatin and vincristine. No AEs were collected during this period	LGG Cohort: Carboplatin and Vincristine (Crossover On-treatment) n=12 participants at risk AEs collected during crossover on-treatment period with dabrafenib and trametinib for participants in the LGG cohort randomized to carboplatin and vincristine who crossedover to dabrafenib and trametinib after disease progression (up to 30 days post- crossover treatment)	LGG Cohort: Carboplatin and Vincristine (Crossover Post-treatment Follow-up) Deaths collected in the crossover post- treatment follow-up period (starting from day 31 post- crossover treatment) for participants in the LGG cohort treated with carboplatin and vincristine who crossed over to dabrafenib and trametinib. No AEs were collected during this period
Blood and lymphatic system disorders Anaemia	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Cardiac disorders Ventricular enlargement	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/9 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Eye disorders Detachment of retinal pigment epithelium	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Gastrointestinal disorders Ascites	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Gastrointestinal disorders Constipation	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Gastrointestinal disorders Gastrointestinal haemorrhage	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Gastrointestinal disorders Pancreatitis	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Gastrointestinal disorders Vomiting	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	4.1% 3/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
General disorders General physical health deterioration	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/9 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
General disorders Influenza like illness	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
General disorders Malaise	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
General disorders Pain	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
General disorders Pyrexia	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	16.4% 12/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	18.2% 6/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	16.7% 2/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Bacterial sepsis	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Brain abscess	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Bronchitis	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Device related infection	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Encephalomyelitis	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Infection	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Laryngitis	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Sepsis	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/9 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Tonsillitis	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	4.1% 3/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Tooth abscess	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Toxic shock syndrome	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Upper respiratory tract infection	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Urinary tract infection	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Urinary tract infection bacterial	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Varicella	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Viral myositis	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Injury, poisoning and procedural complications Procedural complication	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Injury, poisoning and procedural complications Shunt malfunction	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Injury, poisoning and procedural complications Tooth avulsion	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Investigations C-reactive protein increased	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Investigations Neutrophil count decreased	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/9 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Investigations Oxygen saturation decreased	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Metabolism and nutrition disorders Dehydration	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Altered state of consciousness	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Cerebral haemorrhage	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Cerebral ventricle dilatation	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Vascular disorders Embolism	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Cerebrospinal fluid circulation disorder	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Depressed level of consciousness	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Dizziness	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Dysarthria	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Facial paralysis	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Haemorrhage intracranial	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Headache	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Hemiparesis	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Hydrocephalus	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Intracranial pressure increased	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Ischaemic cerebral infarction	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Migraine with aura	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Paraesthesia	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Paresis	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Partial seizures	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Peripheral motor neuropathy	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Seizure	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Psychiatric disorders Agitation	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Psychiatric disorders Anxiety	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Psychiatric disorders Confusional state	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Psychiatric disorders Mental status changes	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Renal and urinary disorders Renal colic	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Reproductive system and breast disorders Uterine haemorrhage	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Respiratory, thoracic and mediastinal disorders Apnoea	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Respiratory, thoracic and mediastinal disorders Atelectasis	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Erythema nodosum	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Rash	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Vascular disorders Hypotension	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Blood and lymphatic system disorders Febrile neutropenia	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Blood and lymphatic system disorders Neutropenia	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Eye disorders Papilloedema	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Haematological infection	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Pneumonia	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Vulvitis	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Injury, poisoning and procedural complications Fracture	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Injury, poisoning and procedural complications Road traffic accident	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Central nervous system lesion	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Optic perineuritis	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Syncope	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Renal and urinary disorders Nephrolithiasis	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Respiratory, thoracic and mediastinal disorders Tonsillar hypertrophy	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.

Other adverse events

Other adverse events
Measure	HGG Cohort: Dabrafenib and Trametinib (On-treatment) n=41 participants at risk AEs collected during on-treatment period with dabrafenib and trametinib in the HGG cohort (up to 30 days post- treatment)	HGG Cohort: Dabrafenib and Trametinib (Post-treatment Follow-up) Deaths collected in the post- treatment follow-up period for participants in the HGG cohort treated with dabrafenib and trametinib (starting from day 31 post- treatment). No AEs were collected during this period	LGG Cohort: Dabrafenib and Trametinib (On-treatment) n=73 participants at risk AEs collected during on-treatment period with dabrafenib and trametinib in the LGG cohort (up to 30 days post- treatment)	LGG Cohort: Dabrafenib and Trametinib (Post-treatment Follow-up) Deaths collected in the post- treatment follow-up period for participants in the LGG cohort treated with dabrafenib and trametinib (starting from day 31 post- treatment). No AEs were collected during this period	LGG Cohort: Carboplatin and Vincristine (On-treatment) n=33 participants at risk AEs collected during on-treatment period with carboplatin and vincristine in the LGG cohort (up to 30 days post- treatment or start date of crossover treatment, whichever was earlier)	LGG Cohort: Carboplatin and Vincristine (Post-treatment Follow-up) Deaths collected in the post- treatment follow-up period (starting from day 31 post- treatment) for participants in the LGG cohort treated with carboplatin and vincristine. No AEs were collected during this period	LGG Cohort: Carboplatin and Vincristine (Crossover On-treatment) n=12 participants at risk AEs collected during crossover on-treatment period with dabrafenib and trametinib for participants in the LGG cohort randomized to carboplatin and vincristine who crossedover to dabrafenib and trametinib after disease progression (up to 30 days post- crossover treatment)	LGG Cohort: Carboplatin and Vincristine (Crossover Post-treatment Follow-up) Deaths collected in the crossover post- treatment follow-up period (starting from day 31 post- crossover treatment) for participants in the LGG cohort treated with carboplatin and vincristine who crossed over to dabrafenib and trametinib. No AEs were collected during this period
Blood and lymphatic system disorders Anaemia	9.8% 4/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	19.2% 14/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	60.6% 20/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Blood and lymphatic system disorders Leukopenia	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	4.1% 3/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Blood and lymphatic system disorders Lymphopenia	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Blood and lymphatic system disorders Neutropenia	17.1% 7/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	13.7% 10/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	30.3% 10/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Blood and lymphatic system disorders Thrombocytopenia	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	15.2% 5/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Cardiac disorders Aortic valve incompetence	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Ear and labyrinth disorders Vertigo	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Eye disorders Eyelid ptosis	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Gastrointestinal disorders Abdominal pain	12.2% 5/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	20.5% 15/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	21.2% 7/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Gastrointestinal disorders Abdominal pain upper	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	17.8% 13/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Gastrointestinal disorders Angular cheilitis	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Gastrointestinal disorders Aphthous ulcer	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Gastrointestinal disorders Constipation	14.6% 6/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	13.7% 10/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	36.4% 12/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Gastrointestinal disorders Dental caries	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Gastrointestinal disorders Diarrhoea	24.4% 10/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	37.0% 27/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	18.2% 6/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	16.7% 2/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Gastrointestinal disorders Nausea	26.8% 11/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	28.8% 21/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	51.5% 17/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	25.0% 3/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Gastrointestinal disorders Stomatitis	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.2% 6/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	15.2% 5/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Gastrointestinal disorders Vomiting	29.3% 12/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	34.2% 25/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	51.5% 17/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	50.0% 6/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
General disorders Asthenia	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	9.1% 3/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
General disorders Catheter site pain	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
General disorders Chills	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
General disorders Facial pain	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	9.1% 3/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
General disorders Fatigue	14.6% 6/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	34.2% 25/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	30.3% 10/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
General disorders Influenza like illness	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
General disorders Oedema peripheral	9.8% 4/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
General disorders Pyrexia	48.8% 20/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	69.9% 51/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	58.3% 7/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Immune system disorders Hypersensitivity	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	18.2% 6/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations COVID-19	14.6% 6/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	35.6% 26/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	25.0% 3/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Conjunctivitis	9.8% 4/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.2% 6/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Gingivitis	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Nasopharyngitis	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	12.3% 9/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Otitis media	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Paronychia	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	23.3% 17/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Rash pustular	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.2% 6/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Rhinitis	9.8% 4/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	9.6% 7/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	12.1% 4/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	16.7% 2/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Sinusitis	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Upper respiratory tract infection	24.4% 10/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	21.9% 16/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Urinary tract infection	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Injury, poisoning and procedural complications Contusion	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	4.1% 3/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	9.1% 3/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Injury, poisoning and procedural complications Head injury	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	15.2% 5/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Investigations Alanine aminotransferase increased	9.8% 4/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	13.7% 10/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	27.3% 9/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	16.7% 2/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Investigations Aspartate aminotransferase increased	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	12.3% 9/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	15.2% 5/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	25.0% 3/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Investigations Blood alkaline phosphatase increased	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	9.6% 7/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Investigations Blood bicarbonate decreased	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	9.1% 3/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Investigations Ejection fraction decreased	9.8% 4/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Investigations Lymphocyte count decreased	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.8% 5/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	15.2% 5/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Investigations Neutrophil count decreased	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	15.1% 11/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	48.5% 16/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	16.7% 2/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Investigations Platelet count decreased	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	30.3% 10/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Investigations SARS-CoV-2 test negative	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	16.7% 2/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Investigations Weight decreased	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	12.1% 4/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Investigations Weight increased	14.6% 6/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	16.4% 12/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Investigations White blood cell count decreased	12.2% 5/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	12.3% 9/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	36.4% 12/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Metabolism and nutrition disorders Cerebral salt-wasting syndrome	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Metabolism and nutrition disorders Decreased appetite	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	24.2% 8/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Metabolism and nutrition disorders Hyperglycaemia	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	9.1% 3/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Metabolism and nutrition disorders Hyperkalaemia	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Metabolism and nutrition disorders Hypernatraemia	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	4.1% 3/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Metabolism and nutrition disorders Hypocalcaemia	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	12.1% 4/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Metabolism and nutrition disorders Hypokalaemia	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	4.1% 3/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	12.1% 4/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	18.2% 6/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Metabolism and nutrition disorders Hyponatraemia	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Metabolism and nutrition disorders Hypophosphataemia	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	9.1% 3/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Metabolism and nutrition disorders Obesity	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Musculoskeletal and connective tissue disorders Arthralgia	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	12.3% 9/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	16.7% 2/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Musculoskeletal and connective tissue disorders Back pain	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	9.6% 7/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	12.1% 4/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Musculoskeletal and connective tissue disorders Myalgia	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	9.6% 7/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	9.1% 3/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Musculoskeletal and connective tissue disorders Pain in extremity	9.8% 4/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	17.8% 13/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	12.1% 4/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	18.2% 6/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	16.7% 2/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	9.8% 4/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	13.7% 10/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Dizziness	9.8% 4/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	11.0% 8/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Headache	41.5% 17/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	53.4% 39/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	24.2% 8/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	58.3% 7/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Neuralgia	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	9.1% 3/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Paraesthesia	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.8% 5/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	9.1% 3/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Peripheral motor neuropathy	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	15.2% 5/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	15.2% 5/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Seizure	12.2% 5/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Product Issues Device malfunction	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Psychiatric disorders Anxiety	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	15.2% 5/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Psychiatric disorders Intentional self-injury	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Renal and urinary disorders Haematuria	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	4.1% 3/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Renal and urinary disorders Proteinuria	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Respiratory, thoracic and mediastinal disorders Cough	17.1% 7/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	15.1% 11/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	12.1% 4/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	25.0% 3/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Respiratory, thoracic and mediastinal disorders Epistaxis	14.6% 6/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	21.9% 16/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	16.7% 2/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Respiratory, thoracic and mediastinal disorders Nasal congestion	9.8% 4/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	4.1% 3/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	16.7% 2/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	14.6% 6/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	13.7% 10/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	21.2% 7/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	33.3% 4/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	4.1% 3/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	12.1% 4/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	16.7% 2/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Acne	14.6% 6/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	13.7% 10/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Alopecia	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	27.3% 9/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Dermatitis	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Dermatitis acneiform	9.8% 4/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	13.7% 10/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	16.7% 2/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Dry skin	34.1% 14/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	27.4% 20/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Eczema	12.2% 5/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	17.8% 13/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Erythema	12.2% 5/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	16.4% 12/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Erythema nodosum	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.8% 5/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Hand dermatitis	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Ingrowing nail	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Keratosis pilaris	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Panniculitis	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.2% 6/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Papule	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	16.7% 2/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Pruritus	9.8% 4/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	12.3% 9/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Rash	22.0% 9/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	19.2% 14/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	9.1% 3/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Rash maculo-papular	14.6% 6/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	17.8% 13/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Skin striae	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.8% 5/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Urticaria	12.2% 5/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.2% 6/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Vascular disorders Hypertension	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/9 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Ear and labyrinth disorders Ear pain	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Endocrine disorders Growth hormone deficiency	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	16.7% 2/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Endocrine disorders Thyroid disorder	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Eye disorders Dry eye	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Eye disorders Eye pain	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	4.1% 3/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Eye disorders Uveitis	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Eye disorders Vision blurred	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.2% 6/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Gastrointestinal disorders Dyspepsia	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Gastrointestinal disorders Food poisoning	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Gastrointestinal disorders Toothache	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
General disorders Cyst	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
General disorders Gait disturbance	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
General disorders Hyperpyrexia	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
General disorders Malaise	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
General disorders Non-cardiac chest pain	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	16.7% 2/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Bronchitis	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Ear infection	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Folliculitis	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	4.1% 3/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Fungal skin infection	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Gastroenteritis	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Oral candidiasis	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Pharyngitis	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.2% 6/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Pulpitis dental	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Respiratory tract infection	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Respiratory tract infection viral	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Tinea manuum	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Tonsillitis	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Vaginal infection	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Infections and infestations Viral infection	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Injury, poisoning and procedural complications Arthropod bite	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Injury, poisoning and procedural complications Ligament sprain	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.2% 6/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Investigations Blood pressure decreased	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Investigations SARS-CoV-2 test positive	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.2% 6/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Investigations Streptococcus test positive	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Metabolism and nutrition disorders Vitamin D deficiency	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Musculoskeletal and connective tissue disorders Immobilisation syndrome	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Ataxia	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Neuropathy peripheral	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Nervous system disorders Presyncope	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	16.7% 2/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Psychiatric disorders Insomnia	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Psychiatric disorders Mental status changes	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Psychiatric disorders Somatic symptom disorder	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Reproductive system and breast disorders Pelvic pain	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Respiratory, thoracic and mediastinal disorders Snoring	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Respiratory, thoracic and mediastinal disorders Tonsillar hypertrophy	2.4% 1/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Dermatitis contact	7.3% 3/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Dyshidrotic eczema	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	1.4% 1/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Erythema multiforme	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	2.7% 2/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	6.1% 2/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Hyperkeratosis	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	4.1% 3/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	3.0% 1/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Rash erythematous	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.
Skin and subcutaneous tissue disorders Skin lesion	4.9% 2/41 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	5.5% 4/73 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	0.00% 0/33 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	8.3% 1/12 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.	— 0/0 • On-treatment AEs: from first dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment deaths: from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG).Crossover on-treatment: AEs from first dose to 30 days after last dose of crossover treatment, up to 4.2 years. Deaths in the post treatment follow-up period are not considered Adverse Events. The total number at risk in the post treatment includes patients that entered the post treatment follow-up period (post-treatment efficacy and/or survival follow-up). Analysis performed in the safety set including participants who received at least one dose of study treatment. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up.

Additional Information

Study director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER