Trial Outcomes & Findings for Testing the Use of the Immunotherapy Drugs Ipilimumab and Nivolumab Plus Radiation Therapy Compared to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed MGMT Unmethylated Glioblastoma (NCT NCT04396860)

NCT ID: NCT04396860

Last Updated: 2025-12-18

Results Overview

Disease progression was confirmed by central review and defined using an adaptation of the Response Assessment in Neuro-Oncology criteria (Wen et al, J Clin Oncol. 2010 Apr 10;28(11):1963-72. doi: 10.1200/JCO.2009.26.3541. Epub 2010 Mar 15) with modification such that the first MRI performed following completion of radiotherapy is the baseline MRI for determination of radiographic disease. Progression-free survival time is defined as time from randomization to the date of first progression, death, or the last progression assessment with no documented progression (censored). Progression-free survival rates were estimated using the Kaplan-Meier method.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE2/PHASE3
• Target enrollment: 159 participants
• Primary outcome timeframe: From randomization to date of progression, death, or last known follow-up, whichever occurs first. Maximum follow-up time was 19.3 months.
• Results posted on: 2025-12-18

Participant Flow

Screening required central pathology review confirmation of glioblastoma histology and unmethylated MGMT promotor status in order to proceed to randomization. Of 374 patients registered, 159 patients were randomized.

Participant milestones

Measure	Arm I (Radiation Therapy, Temozolomide) Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks and simultaneously receive temozolomide PO daily for 6 weeks. After radiation, patients may wear the Optune device at the discretion of the patient and their treating physician. Beginning 1 month after radiation therapy, patients receive temozolomide on days 1-5. Treatment repeats every 28 days for up to 12 cycles at the discretion of the treating investigator in the absence of disease progression or unacceptable toxicity. Patients also undergo contrast-enhanced brain MRI throughout the trial.	Arm II (Radiation Therapy, Ipilimumab, Nivolumab) Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks. Starting on the first day of radiation, patients also receive ipilimumab IV over 90 minutes Q4W for 4 doses and nivolumab IV over 30 minutes every 2 weeks until disease progression. Patients also undergo contrast-enhanced brain MRI throughout the trial.
Overall Study STARTED	80	79
Overall Study Randomized	80	79
Overall Study Adverse Event Population	74	78
Overall Study COMPLETED	80	79
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Testing the Use of the Immunotherapy Drugs Ipilimumab and Nivolumab Plus Radiation Therapy Compared to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed MGMT Unmethylated Glioblastoma

Baseline characteristics by cohort

Measure	Arm I (Radiation Therapy, Temozolomide) n=80 Participants Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks and simultaneously receive temozolomide PO daily for 6 weeks. After radiation, patients may wear the Optune device at the discretion of the patient and their treating physician. Beginning 1 month after radiation therapy, patients receive temozolomide on days 1-5. Treatment repeats every 28 days for up to 12 cycles at the discretion of the treating investigator in the absence of disease progression or unacceptable toxicity. Patients also undergo contrast-enhanced brain MRI throughout the trial. Contrast-enhanced Magnetic Resonance Imaging: Undergo contrast-enhanced brain MRI NovoTTF-100A Device: Wear Optune device Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Radiation Therapy: Undergo radiation therapy Temozolomide: Given PO	Arm II (Radiation Therapy, Ipilimumab, Nivolumab) n=79 Participants Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks. Starting on the first day of radiation, patients also receive ipilimumab IV over 90 minutes Q4W for 4 doses and nivolumab IV over 30 minutes every 2 weeks until disease progression. Patients also undergo contrast-enhanced brain MRI throughout the trial. Contrast-enhanced Magnetic Resonance Imaging: Undergo contrast-enhanced brain MRI Ipilimumab: Given IV Nivolumab: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Radiation Therapy: Undergo radiation therapy	Total n=159 Participants Total of all reporting groups
Age, Continuous	59.5 years n=47 Participants	61 years n=41 Participants	60 years n=88 Participants
Age, Customized ≤ 49	15 Participants n=47 Participants	9 Participants n=41 Participants	24 Participants n=88 Participants
Age, Customized 50 -59	25 Participants n=47 Participants	27 Participants n=41 Participants	52 Participants n=88 Participants
Age, Customized 60 -69	30 Participants n=47 Participants	27 Participants n=41 Participants	57 Participants n=88 Participants
Age, Customized ≥ 70	10 Participants n=47 Participants	16 Participants n=41 Participants	26 Participants n=88 Participants
Sex: Female, Male Female	26 Participants n=47 Participants	28 Participants n=41 Participants	54 Participants n=88 Participants
Sex: Female, Male Male	54 Participants n=47 Participants	51 Participants n=41 Participants	105 Participants n=88 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=47 Participants	9 Participants n=41 Participants	16 Participants n=88 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	73 Participants n=47 Participants	69 Participants n=41 Participants	142 Participants n=88 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=47 Participants	1 Participants n=41 Participants	1 Participants n=88 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=47 Participants	0 Participants n=41 Participants	0 Participants n=88 Participants
Race (NIH/OMB) Asian	3 Participants n=47 Participants	4 Participants n=41 Participants	7 Participants n=88 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=47 Participants	0 Participants n=41 Participants	0 Participants n=88 Participants
Race (NIH/OMB) Black or African American	1 Participants n=47 Participants	2 Participants n=41 Participants	3 Participants n=88 Participants
Race (NIH/OMB) White	71 Participants n=47 Participants	69 Participants n=41 Participants	140 Participants n=88 Participants
Race (NIH/OMB) More than one race	0 Participants n=47 Participants	0 Participants n=41 Participants	0 Participants n=88 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=47 Participants	4 Participants n=41 Participants	9 Participants n=88 Participants
Karnofsky performance status (KPS) 70	10 Participants n=47 Participants	6 Participants n=41 Participants	16 Participants n=88 Participants
Karnofsky performance status (KPS) 80	24 Participants n=47 Participants	22 Participants n=41 Participants	46 Participants n=88 Participants
Karnofsky performance status (KPS) 90	37 Participants n=47 Participants	36 Participants n=41 Participants	73 Participants n=88 Participants
Karnofsky performance status (KPS) 100	9 Participants n=47 Participants	15 Participants n=41 Participants	24 Participants n=88 Participants
Extent of resection Biopsy	1 Participants n=47 Participants	0 Participants n=41 Participants	1 Participants n=88 Participants
Extent of resection Subtotal	28 Participants n=47 Participants	27 Participants n=41 Participants	55 Participants n=88 Participants
Extent of resection Total (gross)	51 Participants n=47 Participants	52 Participants n=41 Participants	103 Participants n=88 Participants
Neurologic function No symptoms	22 Participants n=47 Participants	37 Participants n=41 Participants	59 Participants n=88 Participants
Neurologic function Minor symptoms	44 Participants n=47 Participants	27 Participants n=41 Participants	71 Participants n=88 Participants
Neurologic function Moderate symptoms (fully active)	11 Participants n=47 Participants	10 Participants n=41 Participants	21 Participants n=88 Participants
Neurologic function Moderate symptoms (required assistance)	3 Participants n=47 Participants	5 Participants n=41 Participants	8 Participants n=88 Participants
Recursive partitioning analysis (RPA) class III	9 Participants n=47 Participants	7 Participants n=41 Participants	16 Participants n=88 Participants
Recursive partitioning analysis (RPA) class IV	58 Participants n=47 Participants	58 Participants n=41 Participants	116 Participants n=88 Participants
Recursive partitioning analysis (RPA) class V	13 Participants n=47 Participants	14 Participants n=41 Participants	27 Participants n=88 Participants
Intent to use Optune No	42 Participants n=47 Participants	41 Participants n=41 Participants	83 Participants n=88 Participants
Intent to use Optune Yes	38 Participants n=47 Participants	38 Participants n=41 Participants	76 Participants n=88 Participants

PRIMARY outcome

Timeframe: From randomization to date of progression, death, or last known follow-up, whichever occurs first. Maximum follow-up time was 19.3 months.

Population: Randomized participants

Disease progression was confirmed by central review and defined using an adaptation of the Response Assessment in Neuro-Oncology criteria (Wen et al, J Clin Oncol. 2010 Apr 10;28(11):1963-72. doi: 10.1200/JCO.2009.26.3541. Epub 2010 Mar 15) with modification such that the first MRI performed following completion of radiotherapy is the baseline MRI for determination of radiographic disease. Progression-free survival time is defined as time from randomization to the date of first progression, death, or the last progression assessment with no documented progression (censored). Progression-free survival rates were estimated using the Kaplan-Meier method.

Outcome measures

Measure	Arm I (Radiation Therapy, Temozolomide) n=80 Participants Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks and simultaneously receive temozolomide PO daily for 6 weeks. After radiation, patients may wear the Optune device at the discretion of the patient and their treating physician. Beginning 1 month after radiation therapy, patients receive temozolomide on days 1-5. Treatment repeats every 28 days for up to 12 cycles at the discretion of the treating investigator in the absence of disease progression or unacceptable toxicity. Patients also undergo contrast-enhanced brain MRI throughout the trial.	Arm II (Radiation Therapy, Ipilimumab, Nivolumab) n=79 Participants Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks. Starting on the first day of radiation, patients also receive ipilimumab IV over 90 minutes Q4W for 4 doses and nivolumab IV over 30 minutes every 2 weeks until disease progression. Patients also undergo contrast-enhanced brain MRI throughout the trial.
Progression-free Survival (PFS) (Phase II)	8.5 months Interval 7.1 to 10.4	7.7 months Interval 6.5 to 8.5

PRIMARY outcome

Timeframe: From randomization to date of death or last known follow-up. Maximum follow-up time was 19.3 months.

Population: Study did not continue to the Phase III component.

Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates were to be estimated by the Kaplan-Meier method.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From randomization to date of progression, death, or last known follow-up. Maximum follow-up time was 19.3 months.

Population: Study did not continue to the Phase III component.

Disease progression was confirmed by central review and defined using an adaptation of the Response Assessment in Neuro-Oncology criteria (Wen et al, J Clin Oncol. 2010 Apr 10;28(11):1963-72. doi: 10.1200/JCO.2009.26.3541. Epub 2010 Mar 15) with modification such that the first MRI performed following completion of radiotherapy is the baseline MRI for determination of radiographic disease. Progression-free survival time is defined as time from randomization to the date of first progression, death, or the last progression assessment with no documented progression (censored). Progression-free survival rates were estimated using the Kaplan-Meier method.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From randomization to two years

Population: Study did not continue to the Phase III component.

Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Two-year survival rates were to be estimated by the Kaplan-Meier method.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From randomization to date of last known follow-up. Maximum follow-up time was 19.3 months.

Population: Randomized participants who started protocol treatment and were assessed for adverse events.

Common Terminology Criteria for Adverse Events (version 5.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.

Outcome measures

Measure	Arm I (Radiation Therapy, Temozolomide) n=74 Participants Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks and simultaneously receive temozolomide PO daily for 6 weeks. After radiation, patients may wear the Optune device at the discretion of the patient and their treating physician. Beginning 1 month after radiation therapy, patients receive temozolomide on days 1-5. Treatment repeats every 28 days for up to 12 cycles at the discretion of the treating investigator in the absence of disease progression or unacceptable toxicity. Patients also undergo contrast-enhanced brain MRI throughout the trial.	Arm II (Radiation Therapy, Ipilimumab, Nivolumab) n=78 Participants Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks. Starting on the first day of radiation, patients also receive ipilimumab IV over 90 minutes Q4W for 4 doses and nivolumab IV over 30 minutes every 2 weeks until disease progression. Patients also undergo contrast-enhanced brain MRI throughout the trial.
Number of Participants by Highest Grade Adverse Event Reported Grade 1	6 Participants	1 Participants
Number of Participants by Highest Grade Adverse Event Reported Grade 2	19 Participants	21 Participants
Number of Participants by Highest Grade Adverse Event Reported Grade 3	38 Participants	38 Participants
Number of Participants by Highest Grade Adverse Event Reported Grade 4	9 Participants	10 Participants
Number of Participants by Highest Grade Adverse Event Reported Grade 5	0 Participants	4 Participants

SECONDARY outcome

Timeframe: Up to 2 years

The MD Anderson Symptom Inventory for brain tumor (MDASI-BT) is a 28-item multi-symptom patient-reported outcome measure assessing the severity of symptoms experienced by cancer patients and the interference with daily living caused by these symptoms, with 9 items specific to brain tumors. Each item ranges from 0 (best condition) to 10 (worst condition). A subscale score is the average of the subscale items, given that a specified minimum numbers of items were completed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 2 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 2 years

Questions refer to the participants' experiences for the past 7 days of a given symptom in terms of frequency (never, rarely, occasionally, frequently, almost constantly), severity (none, mild, moderate, severe, very severe), interference with usual or daily activities (not at all, a little bit, somewhat, quite a bit, very much).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At the end of phase II of study

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 4 years

Will assess PD-L1 expression and mutational burden expression specifically.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 4 years

Will assess the prognostic value of MGMT protein expression (in terms of predicting clinical outcomes such as PFS, OS, and 2-year OS rate) in the two treatment arms, separately. In addition, will evaluate if MGMT protein expression may be predictive of differential treatment effects between the two treatment arms. Correlation methods and survival modeling will be used to address these questions.

Outcome measures

Outcome data not reported

Adverse Events

Arm I (Radiation Therapy, Temozolomide)

Serious events: 29 serious events

Other events: 70 other events

Deaths: 41 deaths

Arm II (Radiation Therapy, Ipilimumab, Nivolumab)

Serious events: 45 serious events

Other events: 70 other events

Deaths: 37 deaths

Serious adverse events

Measure	Arm I (Radiation Therapy, Temozolomide) n=74 participants at risk Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks and simultaneously receive temozolomide PO daily for 6 weeks. After radiation, patients may wear the Optune device at the discretion of the patient and their treating physician. Beginning 1 month after radiation therapy, patients receive temozolomide on days 1-5. Treatment repeats every 28 days for up to 12 cycles at the discretion of the treating investigator in the absence of disease progression or unacceptable toxicity. Patients also undergo contrast-enhanced brain MRI throughout the trial.	Arm II (Radiation Therapy, Ipilimumab, Nivolumab) n=78 participants at risk Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks. Starting on the first day of radiation, patients also receive ipilimumab IV over 90 minutes Q4W for 4 doses and nivolumab IV over 30 minutes every 2 weeks until disease progression. Patients also undergo contrast-enhanced brain MRI throughout the trial.
Cardiac disorders Cardiac disorders - Other	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Endocrine disorders Hyperthyroidism	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Endocrine disorders Hypophysitis	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Gastrointestinal disorders Abdominal pain	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Gastrointestinal disorders Colitis	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Gastrointestinal disorders Colonic perforation	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Gastrointestinal disorders Constipation	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Gastrointestinal disorders Diarrhea	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Gastrointestinal disorders Enterocolitis	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Gastrointestinal disorders Gastrointestinal disorders - Other	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Gastrointestinal disorders Ileus	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Gastrointestinal disorders Nausea	4.1% 3/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Gastrointestinal disorders Vomiting	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
General disorders Chills	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
General disorders Disease progression	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
General disorders Edema limbs	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
General disorders Fatigue	2.7% 2/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
General disorders Fever	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	2.6% 2/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
General disorders Gait disturbance	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
General disorders General disorders and administration site conditions - Other	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Immune system disorders Autoimmune disorder	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	2.6% 2/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Infections and infestations Bone infection	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Infections and infestations Encephalitis infection	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Infections and infestations Infections and infestations - Other	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Infections and infestations Lung infection	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Infections and infestations Meningitis	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Infections and infestations Sepsis	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	3.8% 3/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Infections and infestations Sinusitis	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Infections and infestations Urinary tract infection	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Infections and infestations Wound infection	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Injury, poisoning and procedural complications Fall	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Injury, poisoning and procedural complications Wound dehiscence	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Investigations Alanine aminotransferase increased	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Investigations Blood bilirubin increased	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Investigations Platelet count decreased	2.7% 2/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Investigations White blood cell decreased	2.7% 2/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Metabolism and nutrition disorders Dehydration	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Metabolism and nutrition disorders Hyperglycemia	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	2.7% 2/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	2.6% 2/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Ataxia	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Cognitive disturbance	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Dizziness	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Dysgeusia	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Dysphasia	2.7% 2/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Edema cerebral	4.1% 3/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	3.8% 3/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Encephalopathy	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	6.4% 5/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Headache	2.7% 2/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Hydrocephalus	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Intracranial hemorrhage	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Muscle weakness left-sided	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Nervous system disorders - Other	2.7% 2/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	2.6% 2/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Paresthesia	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	2.6% 2/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Seizure	6.8% 5/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	12.8% 10/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Stroke	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Syncope	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Psychiatric disorders Anxiety	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Psychiatric disorders Confusion	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	3.8% 3/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Psychiatric disorders Delirium	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Psychiatric disorders Mania	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Renal and urinary disorders Bladder perforation	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	2.6% 2/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Vascular disorders Hypotension	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Vascular disorders Thromboembolic event	2.7% 2/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	7.7% 6/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.

Other adverse events

Measure	Arm I (Radiation Therapy, Temozolomide) n=74 participants at risk Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks and simultaneously receive temozolomide PO daily for 6 weeks. After radiation, patients may wear the Optune device at the discretion of the patient and their treating physician. Beginning 1 month after radiation therapy, patients receive temozolomide on days 1-5. Treatment repeats every 28 days for up to 12 cycles at the discretion of the treating investigator in the absence of disease progression or unacceptable toxicity. Patients also undergo contrast-enhanced brain MRI throughout the trial.	Arm II (Radiation Therapy, Ipilimumab, Nivolumab) n=78 participants at risk Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks. Starting on the first day of radiation, patients also receive ipilimumab IV over 90 minutes Q4W for 4 doses and nivolumab IV over 30 minutes every 2 weeks until disease progression. Patients also undergo contrast-enhanced brain MRI throughout the trial.
Gastrointestinal disorders Diarrhea	10.8% 8/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	29.5% 23/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Ear and labyrinth disorders Tinnitus	5.4% 4/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	2.6% 2/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Endocrine disorders Hyperthyroidism	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	9.0% 7/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Endocrine disorders Hypothyroidism	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	11.5% 9/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Eye disorders Blurred vision	10.8% 8/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	10.3% 8/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Eye disorders Dry eye	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	7.7% 6/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Eye disorders Eye disorders - Other	4.1% 3/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	10.3% 8/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Gastrointestinal disorders Abdominal pain	12.2% 9/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	9.0% 7/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Gastrointestinal disorders Colitis	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Gastrointestinal disorders Constipation	45.9% 34/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	20.5% 16/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Blood and lymphatic system disorders Anemia	28.4% 21/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	33.3% 26/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Cardiac disorders Sinus tachycardia	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Gastrointestinal disorders Dry mouth	8.1% 6/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	7.7% 6/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Gastrointestinal disorders Dysphagia	9.5% 7/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Gastrointestinal disorders Mucositis oral	5.4% 4/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	6.4% 5/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Gastrointestinal disorders Nausea	43.2% 32/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	38.5% 30/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Gastrointestinal disorders Vomiting	16.2% 12/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	20.5% 16/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
General disorders Chills	5.4% 4/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	10.3% 8/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
General disorders Edema face	6.8% 5/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	7.7% 6/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
General disorders Edema limbs	16.2% 12/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	11.5% 9/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
General disorders Fatigue	68.9% 51/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	64.1% 50/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
General disorders Fever	2.7% 2/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	11.5% 9/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
General disorders Gait disturbance	12.2% 9/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	16.7% 13/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
General disorders Malaise	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
General disorders Non-cardiac chest pain	1.4% 1/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
General disorders Pain	8.1% 6/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	9.0% 7/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Infections and infestations Infections and infestations - Other	10.8% 8/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	7.7% 6/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Infections and infestations Thrush	6.8% 5/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	10.3% 8/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Infections and infestations Urinary tract infection	2.7% 2/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Injury, poisoning and procedural complications Dermatitis radiation	21.6% 16/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	16.7% 13/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Injury, poisoning and procedural complications Fall	13.5% 10/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	6.4% 5/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Investigations Alanine aminotransferase increased	21.6% 16/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	29.5% 23/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Investigations Alkaline phosphatase increased	6.8% 5/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	7.7% 6/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Investigations Aspartate aminotransferase increased	12.2% 9/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	28.2% 22/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Investigations Blood bilirubin increased	13.5% 10/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	3.8% 3/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Investigations Blood lactate dehydrogenase increased	2.7% 2/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Investigations Creatinine increased	12.2% 9/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	10.3% 8/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Investigations Investigations - Other	6.8% 5/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Investigations Lipase increased	4.1% 3/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Investigations Lymphocyte count decreased	45.9% 34/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	23.1% 18/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Investigations Neutrophil count decreased	10.8% 8/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	11.5% 9/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Investigations Platelet count decreased	32.4% 24/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	14.1% 11/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Investigations Thyroid stimulating hormone increased	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Investigations Weight loss	13.5% 10/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	23.1% 18/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Investigations White blood cell decreased	18.9% 14/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	15.4% 12/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Metabolism and nutrition disorders Anorexia	32.4% 24/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	30.8% 24/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Metabolism and nutrition disorders Dehydration	2.7% 2/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	10.3% 8/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Metabolism and nutrition disorders Hypercalcemia	2.7% 2/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Metabolism and nutrition disorders Hyperglycemia	31.1% 23/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	33.3% 26/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Metabolism and nutrition disorders Hyperkalemia	5.4% 4/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Metabolism and nutrition disorders Hypernatremia	8.1% 6/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	2.6% 2/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Metabolism and nutrition disorders Hypoalbuminemia	13.5% 10/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	16.7% 13/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Metabolism and nutrition disorders Hypocalcemia	9.5% 7/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	9.0% 7/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Metabolism and nutrition disorders Hypoglycemia	8.1% 6/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	2.6% 2/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Metabolism and nutrition disorders Hypokalemia	12.2% 9/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	16.7% 13/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Metabolism and nutrition disorders Hyponatremia	17.6% 13/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	25.6% 20/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	8.1% 6/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	6.4% 5/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Musculoskeletal and connective tissue disorders Back pain	2.7% 2/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	11.5% 9/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	14.9% 11/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	23.1% 18/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	5.4% 4/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other	6.8% 5/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	3.8% 3/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Musculoskeletal and connective tissue disorders Myalgia	5.4% 4/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	3.8% 3/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Musculoskeletal and connective tissue disorders Pain in extremity	8.1% 6/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	7.7% 6/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Ataxia	8.1% 6/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Cognitive disturbance	8.1% 6/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Concentration impairment	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Dizziness	18.9% 14/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	21.8% 17/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Dysarthria	4.1% 3/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Dysgeusia	13.5% 10/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	12.8% 10/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Dysphasia	17.6% 13/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Edema cerebral	4.1% 3/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Headache	44.6% 33/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	39.7% 31/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Memory impairment	16.2% 12/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	16.7% 13/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Muscle weakness left-sided	10.8% 8/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	9.0% 7/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Nervous system disorders - Other	12.2% 9/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	6.4% 5/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Seizure	20.3% 15/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	17.9% 14/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Nervous system disorders Tremor	8.1% 6/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	12.8% 10/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Psychiatric disorders Agitation	5.4% 4/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	3.8% 3/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Psychiatric disorders Anxiety	8.1% 6/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	7.7% 6/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Psychiatric disorders Confusion	13.5% 10/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	16.7% 13/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Psychiatric disorders Depression	6.8% 5/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	9.0% 7/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Psychiatric disorders Insomnia	25.7% 19/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	17.9% 14/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Psychiatric disorders Personality change	5.4% 4/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	0.00% 0/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Renal and urinary disorders Urinary frequency	5.4% 4/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	1.3% 1/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Renal and urinary disorders Urinary incontinence	5.4% 4/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	2.6% 2/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Respiratory, thoracic and mediastinal disorders Cough	12.2% 9/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	16.7% 13/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.8% 5/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	7.7% 6/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Skin and subcutaneous tissue disorders Alopecia	45.9% 34/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	37.2% 29/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Skin and subcutaneous tissue disorders Dry skin	5.4% 4/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	11.5% 9/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Skin and subcutaneous tissue disorders Pruritus	10.8% 8/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	28.2% 22/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Skin and subcutaneous tissue disorders Rash acneiform	0.00% 0/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	5.1% 4/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Skin and subcutaneous tissue disorders Rash maculo-papular	9.5% 7/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	20.5% 16/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	10.8% 8/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	10.3% 8/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Vascular disorders Hypertension	12.2% 9/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	19.2% 15/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Vascular disorders Hypotension	6.8% 5/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	6.4% 5/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.
Vascular disorders Thromboembolic event	9.5% 7/74 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.	10.3% 8/78 • Randomization to date of last known follow-up. Maximum follow-up time was 19.3 months. All-cause mortality was assessed in randomized participants. Adverse events were assessed in randomized participants who started protocol treatment and were assessed for adverse events.

Additional Information

Wendy Seiferheld

NRG Oncology

Phone: 2155743208

Email: seiferheldw@nrgoncology.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60