Trial Outcomes & Findings for PDR001 Plus LAG525 for Patients With Advanced Solid and Hematologic Malignancies (NCT NCT03365791)

NCT ID: NCT03365791

Last Updated: 2022-05-27

Results Overview

CBR is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR) and Stable Disease (SD). Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression. CBR (CR+PR+SD) is reported overall and by tumor type.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 76 participants
• Primary outcome timeframe: 24 weeks
• Results posted on: 2022-05-27

Participant Flow

Participants took part in 20 investigative sites in 1 country (United States).

The screening period began once patients had signed the study informed consent. All screening evaluations were performed as closely as possible to the beginning of treatment and never more than 21 days prior to starting study treatment. After screening, the treatment period started on Cycle 1 Day 1.

Participant milestones

Measure	PDR001+LAG525 PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001.
Overall Study STARTED	76
Overall Study Full Analysis Set (FAS)	75
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	72

Reasons for withdrawal

Measure	PDR001+LAG525 PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001.
Overall Study Adverse Event	5
Overall Study Death	1
Overall Study Lost to Follow-up	1
Overall Study Physician Decision	9
Overall Study Progressive disease	51
Overall Study Subject/guardian decision	5

Baseline Characteristics

PDR001 Plus LAG525 for Patients With Advanced Solid and Hematologic Malignancies

Baseline characteristics by cohort

Measure	PDR001+LAG525 n=76 Participants PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001.
Age, Continuous	65.1 years STANDARD_DEVIATION 10.57 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants
Sex: Female, Male Male	45 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	67 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: Full Analysis Set (FAS)

CBR is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR) and Stable Disease (SD). Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007).

For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.

CBR (CR+PR+SD) is reported overall and by tumor type.

Outcome measures

Measure	PDR001+LAG525 n=75 Participants PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001.
Clinical Benefit Rate (CBR) at 24 Weeks of PDR001+LAG525 by Tumor Type in Multiple Solid Tumors and Lymphoma Overall	25 Participants
Clinical Benefit Rate (CBR) at 24 Weeks of PDR001+LAG525 by Tumor Type in Multiple Solid Tumors and Lymphoma Small cell lung cancer	3 Participants
Clinical Benefit Rate (CBR) at 24 Weeks of PDR001+LAG525 by Tumor Type in Multiple Solid Tumors and Lymphoma Gastric/esophageal adenocarcinoma	2 Participants
Clinical Benefit Rate (CBR) at 24 Weeks of PDR001+LAG525 by Tumor Type in Multiple Solid Tumors and Lymphoma Castration resistant prostate adenocarcinoma (CRPC)	5 Participants
Clinical Benefit Rate (CBR) at 24 Weeks of PDR001+LAG525 by Tumor Type in Multiple Solid Tumors and Lymphoma Soft tissue sarcoma	4 Participants
Clinical Benefit Rate (CBR) at 24 Weeks of PDR001+LAG525 by Tumor Type in Multiple Solid Tumors and Lymphoma Ovarian adenocarcinoma	2 Participants
Clinical Benefit Rate (CBR) at 24 Weeks of PDR001+LAG525 by Tumor Type in Multiple Solid Tumors and Lymphoma Advanced well-differentiated neuroendocrine tumors	6 Participants
Clinical Benefit Rate (CBR) at 24 Weeks of PDR001+LAG525 by Tumor Type in Multiple Solid Tumors and Lymphoma Diffuse large B cell lymphoma (DLBCL)	3 Participants

SECONDARY outcome

Timeframe: From start of treatment until end of treatment, assessed up to 113 weeks

Population: Full Analysis Set (FAS)

ORR is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR). Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007).

For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

ORR (CR+PR) is reported overall (including all tumor types).

Outcome measures

Measure	PDR001+LAG525 n=75 Participants PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001.
Overall Response Rate (ORR)	7 Participants

SECONDARY outcome

Timeframe: From start of treatment to the first documented response of either complete response or partial response, assessed up to 113 weeks

Population: Full Analysis Set (FAS)

TTR is defined as the time from the date of first dose to the date of first documented response of Complete Response (CR) or Partial Response (PR). In case of solid tumor if a patient did not achieve a confirmed response they were censored at maximum follow-up for patients who had a PFS event (progressed or died due to any cause), or at last adequate tumor assessment date otherwise.

Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007).

Outcome measures

Measure	PDR001+LAG525 n=75 Participants PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001.
Time to Response (TTR)	NA months Not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: From first documented response (CR or PR) to first documented progression or death, assessed up to 113 weeks

Population: Participants in the Full Analysis Set (FAS) for whom best overall response is complete response (CR) or partial response (PR)

DOR only applies to subjects for whom best overall response is complete response (CR) or partial response (PR). DOR is defined as the time between the date of first documented response (CR or PR) and the date of first documented progression/relapse or death due to any cause within 150 days of the last study drug dose date. If a patient not had an event, duration was censored at the date of last adequate tumor assessment.

Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007).

Outcome measures

Measure	PDR001+LAG525 n=7 Participants PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001.
Duration of Response (DOR)	NA months Interval 5.8 to Not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: From start of treatment to first documented progression or death due to underlying cancer, assessed up to 113 weeks

Population: Full Analysis Set (FAS)

TTP is the time from start of treatment to the date of event defined as the first documented progression or death due to underlying cancer. If a patient not had an event, time to progression was censored at the date of last adequate tumor assessment.

Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007).

Outcome measures

Measure	PDR001+LAG525 n=75 Participants PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001.
Time to Progression (TTP)	2.8 months Interval 2.7 to 3.8

SECONDARY outcome

Timeframe: From start of treatment to first documented progression or death, assessed up to 113 weeks

Population: Full Analysis Set (FAS)

PFS is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause within 150 days of the last dose. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.

Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007).

Outcome measures

Measure	PDR001+LAG525 n=75 Participants PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001.
Progression-Free Survival (PFS)	2.8 months Interval 2.6 to 3.1

SECONDARY outcome

Timeframe: From first dose of study treatment until last dose of study treatment plus 150 days post treatment, assessed up to 135 weeks.

Population: All participants who received at least one dose of study treatment

Number of participants with AEs and SAEs including changes in laboratory parameters, vital signs and ECGs qualifying and reported as AEs.

Outcome measures

Measure	PDR001+LAG525 n=76 Participants PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	75 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	32 Participants

SECONDARY outcome

Timeframe: From first dose of study treatment until last dose of study treatment, assessed up to 113 weeks.

Population: All participants who received at least one dose of study treatment

Number of participants with at least one dose interruption of PDR001 and LAG525 and number of participants with permanent dose discontinuation of PDR001 and LAG525.

Outcome measures

Measure	PDR001+LAG525 n=76 Participants PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001.
Number of Participants With Dose Interruptions and Permanent Discontinuation of Study Drug PDR001 - dose interruption	30 Participants
Number of Participants With Dose Interruptions and Permanent Discontinuation of Study Drug PDR001 - permanent dose discontinuation	72 Participants
Number of Participants With Dose Interruptions and Permanent Discontinuation of Study Drug LAG525 - dose interruption	30 Participants
Number of Participants With Dose Interruptions and Permanent Discontinuation of Study Drug LAG525 - permanent dose discontinuation	72 Participants

SECONDARY outcome

Timeframe: From first dose of study treatment until last dose of study treatment, assessed up to 113 weeks.

Population: All participants who received at least one dose of study treatment

Dose intensity (mg/day) of PDR001 and LAG525 is calculated as cumulative dose in milligrams divided by duration of exposure in days.

Outcome measures

Measure	PDR001+LAG525 n=76 Participants PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001.
Dose Intensity PDR001	14.1 mg/day Standard Deviation 0.88
Dose Intensity LAG525	18.8 mg/day Standard Deviation 1.20

Adverse Events

PDR001+LAG525 On-treatment Period

Serious events: 31 serious events

Other events: 74 other events

Deaths: 9 deaths

PDR001+LAG525 Extended Safety Follow-up Period

Serious events: 4 serious events

Other events: 12 other events

Deaths: 18 deaths

Serious adverse events

Measure	PDR001+LAG525 On-treatment Period n=76 participants at risk PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001	PDR001+LAG525 Extended Safety Follow-up Period n=76 participants at risk PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001
Blood and lymphatic system disorders Lymphadenopathy	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Cardiac disorders Atrial fibrillation	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Cardiac disorders Atrial flutter	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Cardiac disorders Cardiac failure congestive	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Cardiac disorders Pericardial effusion	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Gastrointestinal disorders Abdominal pain	2.6% 2/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Gastrointestinal disorders Abdominal pain lower	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Gastrointestinal disorders Haematemesis	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Gastrointestinal disorders Nausea	2.6% 2/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Gastrointestinal disorders Vomiting	2.6% 2/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
General disorders Asthenia	3.9% 3/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
General disorders Infusion related reaction	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Hepatobiliary disorders Autoimmune hepatitis	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Infections and infestations Bacteraemia	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Infections and infestations Clostridium difficile infection	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Infections and infestations Enterocolitis infectious	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Infections and infestations Pneumonia	6.6% 5/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Infections and infestations Pyelonephritis	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Infections and infestations Sepsis	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Infections and infestations Urinary tract infection	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Injury, poisoning and procedural complications Fall	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Investigations Alanine aminotransferase increased	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Investigations Aspartate aminotransferase increased	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Investigations Weight decreased	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Metabolism and nutrition disorders Decreased appetite	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Metabolism and nutrition disorders Dehydration	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Metabolism and nutrition disorders Hyponatraemia	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Musculoskeletal and connective tissue disorders Back pain	2.6% 2/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Musculoskeletal and connective tissue disorders Neck pain	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Nervous system disorders Myelitis transverse	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Psychiatric disorders Failure to thrive	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Psychiatric disorders Mental status changes	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Renal and urinary disorders Haematuria	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Renal and urinary disorders Urinary retention	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	2.6% 2/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.6% 2/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Vascular disorders Superior vena cava syndrome	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Cardiac disorders Ventricular extrasystoles	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Nervous system disorders Spinal cord compression	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Renal and urinary disorders Acute kidney injury	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.

Other adverse events

Measure	PDR001+LAG525 On-treatment Period n=76 participants at risk PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001	PDR001+LAG525 Extended Safety Follow-up Period n=76 participants at risk PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001
Blood and lymphatic system disorders Anaemia	17.1% 13/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	2.6% 2/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Cardiac disorders Dizziness	7.9% 6/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	2.6% 2/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Cardiac disorders Dyspnoea	23.7% 18/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Cardiac disorders Oedema peripheral	13.2% 10/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Endocrine disorders Hypercalcaemia	6.6% 5/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Eye disorders Dry eye	5.3% 4/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Gastrointestinal disorders Abdominal distension	10.5% 8/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Gastrointestinal disorders Abdominal pain	18.4% 14/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Gastrointestinal disorders Constipation	26.3% 20/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Gastrointestinal disorders Diarrhoea	19.7% 15/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Gastrointestinal disorders Dry mouth	7.9% 6/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Gastrointestinal disorders Dysgeusia	5.3% 4/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Gastrointestinal disorders Dyspepsia	5.3% 4/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Gastrointestinal disorders Dysphagia	5.3% 4/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Gastrointestinal disorders Flatulence	6.6% 5/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.3% 4/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Gastrointestinal disorders Nausea	34.2% 26/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Gastrointestinal disorders Vomiting	26.3% 20/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
General disorders Chills	7.9% 6/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
General disorders Fatigue	36.8% 28/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
General disorders Non-cardiac chest pain	5.3% 4/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
General disorders Pyrexia	9.2% 7/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Hepatobiliary disorders Ascites	6.6% 5/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Infections and infestations Urinary tract infection	5.3% 4/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Injury, poisoning and procedural complications Fall	9.2% 7/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Investigations Aspartate aminotransferase increased	6.6% 5/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Investigations Blood alkaline phosphatase increased	6.6% 5/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Investigations Blood creatinine increased	13.2% 10/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Investigations Weight decreased	9.2% 7/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Metabolism and nutrition disorders Decreased appetite	28.9% 22/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Metabolism and nutrition disorders Dehydration	11.8% 9/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Metabolism and nutrition disorders Hypomagnesaemia	7.9% 6/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Metabolism and nutrition disorders Hyponatraemia	13.2% 10/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Metabolism and nutrition disorders Hypothyroidism	7.9% 6/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Musculoskeletal and connective tissue disorders Arthralgia	9.2% 7/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Musculoskeletal and connective tissue disorders Back pain	17.1% 13/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Musculoskeletal and connective tissue disorders Muscular weakness	9.2% 7/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	5.3% 4/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	10.5% 8/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Musculoskeletal and connective tissue disorders Myalgia	5.3% 4/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	5.3% 4/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Nervous system disorders Headache	14.5% 11/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Nervous system disorders Insomnia	10.5% 8/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Psychiatric disorders Anxiety	7.9% 6/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Psychiatric disorders Depression	7.9% 6/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Respiratory, thoracic and mediastinal disorders Cough	15.8% 12/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Skin and subcutaneous tissue disorders Dry skin	6.6% 5/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Skin and subcutaneous tissue disorders Pruritus	7.9% 6/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	1.3% 1/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Skin and subcutaneous tissue disorders Rash	11.8% 9/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	7.9% 6/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	2.6% 2/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.
Vascular disorders Hypertension	5.3% 4/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.	0.00% 0/76 • In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: Novartis.email@novartis.com

Results disclosure agreements

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

Restriction type: OTHER