Trial Outcomes & Findings for An Open Label Investigational Immuno-therapy Trial of Nivolumab in Cancers That Are Advanced or Have Spread (NCT NCT02832167)

Last Updated: 2022-05-09

Results Overview

ORR is defined as the percentage of participants with a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR). Best overall response is defined as the best response designation, as determined by investigator, recorded in the specified timeframe, according to the RECIST 1.1 criteria.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

239 participants

Primary outcome timeframe

From first dose to the date of objectively documented progression (per tumor-specific response criteria) or the date of subsequent therapy, whichever occurs first (up to approximately 24 months)

Results posted on

2022-05-09

Participant Flow

239 participants were treated.

Participant milestones

Participant milestones
Measure	Advanced Malignancies Cohort Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Treatment Period 1 STARTED	239
Treatment Period 1 COMPLETED	110
Treatment Period 1 NOT COMPLETED	129
Transition From Period 1 to Period 2 STARTED	110
Transition From Period 1 to Period 2 COMPLETED	103
Transition From Period 1 to Period 2 NOT COMPLETED	7
Treatment Period 2 STARTED	103
Treatment Period 2 COMPLETED	19
Treatment Period 2 NOT COMPLETED	84

Reasons for withdrawal

Reasons for withdrawal
Measure	Advanced Malignancies Cohort Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Treatment Period 1 Disease progression	90
Treatment Period 1 Adverse event unrelated to study drug	12
Treatment Period 1 Death	2
Treatment Period 1 Study Drug Toxicity	6
Treatment Period 1 Participant request to discontinue	9
Treatment Period 1 No longer meet study criteria	1
Treatment Period 1 Participant withdrew consent	3
Treatment Period 1 Other reasons	6
Transition From Period 1 to Period 2 Other reasons	1
Transition From Period 1 to Period 2 Participant withdrew consent	1
Transition From Period 1 to Period 2 Death	2
Transition From Period 1 to Period 2 Lost to Follow-up	3
Treatment Period 2 Disease progression	69
Treatment Period 2 Adverse event unrelated to study drug	1
Treatment Period 2 Maximum clinical benefit	1
Treatment Period 2 Study Drug Toxicity	5
Treatment Period 2 Participant request to discontinue	2
Treatment Period 2 Participant withdrew consent	3
Treatment Period 2 Other reasons	3

Baseline Characteristics

An Open Label Investigational Immuno-therapy Trial of Nivolumab in Cancers That Are Advanced or Have Spread

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Advanced Malignancies Cohort n=239 Participants Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Age, Continuous	59.2 Years STANDARD_DEVIATION 13.79 • n=99 Participants
Sex: Female, Male Female	148 Participants n=99 Participants
Sex: Female, Male Male	91 Participants n=99 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	158 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	70 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	9 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	20 Participants n=99 Participants
Race (NIH/OMB) White	203 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants n=99 Participants

PRIMARY outcome

Timeframe: From first dose to the date of objectively documented progression (per tumor-specific response criteria) or the date of subsequent therapy, whichever occurs first (up to approximately 24 months)

Population: All treated participants

Outcome measures

Outcome measures
Measure	Advanced Malignancies Cohort n=239 Participants Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Objective Response Rate (ORR)	7.9 Percent of Participants Interval 4.9 to 12.1

SECONDARY outcome

Timeframe: From the time of first confirmed response to the date of the first documented progression (up to approximately 22 months)

Population: All Responders (Participants with a confirmed CR or PR)

DOR is defined as the time from first confirmed response (Complete Response, CR or Partial Response, PR) to the date of the first documented tumor progression (as determined by investigator) or death due to any cause, whichever occurs first. Median DOR computed using Kaplan-Meier method

Outcome measures

Outcome measures
Measure	Advanced Malignancies Cohort n=19 Participants Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Duration of Response (DOR)	21.78 Months Interval 2.8 to 22.3

SECONDARY outcome

Timeframe: From the first dosing date to the date of the first confirmed response (up to approximately 10 months)

Population: All Responders (Participants with a confirmed CR or PR)

TTR is defined as the time from first dosing date to the date of the first confirmed response (Complete Response, CR or Partial Response, PR), as assessed by investigator.

Outcome measures

Outcome measures
Measure	Advanced Malignancies Cohort n=19 Participants Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Time to Objective Response (TTR)	3.54 Months Standard Deviation 2.337

SECONDARY outcome

Timeframe: From the first dosing date to the date of the last dose (approximately 24 months)

Population: All treated participants

CBR is defined as the percentage of participants with a best overall response of confirmed Complete Response (CR) or Partial Response (PR) or Stable Disease (SD).

Outcome measures

Outcome measures
Measure	Advanced Malignancies Cohort n=239 Participants Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Clinical Benefit Rate (CBR)	49.8 Percent of participants Interval 43.3 to 56.3

SECONDARY outcome

Timeframe: From the first dosing date to 1 year later

Population: All treated participants

Overall Survival (OS) is defined as the time from the first dosing date to the date of death. A participant who has not died will be censored at last known date alive. OS rate at 1 year is measured as the percent of participants still alive at 1 year after first dosing, measured from Kaplan-Meier curve of OS.

Outcome measures

Outcome measures
Measure	Advanced Malignancies Cohort n=239 Participants Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Overall Survival Rate at 1 Year	56.1 Percent of participants Interval 49.1 to 62.5

SECONDARY outcome

Timeframe: From first dose to 100 days following last dose (up approximately 27 months)

Population: All treated participants

Number of participants who died for any cause

Outcome measures

Outcome measures
Measure	Advanced Malignancies Cohort n=239 Participants Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Number of Participants Who Died	72 Participants

SECONDARY outcome

Timeframe: From first dose to 30 days following the last dose (up to approximately 25 months)

Population: All treated participants

Number of participants who experienced any grade, any cause AEs

Outcome measures

Outcome measures
Measure	Advanced Malignancies Cohort n=239 Participants Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Number of Participants Experiencing Adverse Events (AEs)	234 Participants

SECONDARY outcome

Timeframe: From first dose to 100 days following the last dose (up to approximately 27 months)

Population: All treated participants

Number of participants who experienced any grade, any cause SAEs

Outcome measures

Outcome measures
Measure	Advanced Malignancies Cohort n=239 Participants Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Number of Participants Experiencing Serious Adverse Events (SAEs)	148 Participants

SECONDARY outcome

Timeframe: From first dose to 30 days following the last dose (up to approximately 25 months)

Population: All treated participants

Number of participants who experienced AEs leading to discontinuation of study therapy

Outcome measures

Outcome measures
Measure	Advanced Malignancies Cohort n=239 Participants Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation	41 Participants

SECONDARY outcome

Timeframe: From first dose to 100 days following the last dose (up to approximately 27 months)

Population: All treated participants

Number of participants who experienced IMAEs. IMAEs are AEs consistent with an immune-mediated mechanism or immune-mediated component for which non-inflammatory etiologies (eg, infection or tumor progression) have been ruled out. IMAEs can include events with an alternate etiology which were exacerbated by the induction of autoimmunity.

Outcome measures

Outcome measures
Measure	Advanced Malignancies Cohort n=239 Participants Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Number of Participants Experiencing Immune-mediated Adverse Events (IMAEs)	8 Participants

SECONDARY outcome

Timeframe: From first dose to 30 days following the last dose (up to approximately 25 months)

Population: All treated participants

Number of participants who experienced Select Adverse Events. Select Adverse Events categories include: gastrointestinal, hepatic, pulmonary, renal, skin, hypersensitivity/infusion reaction.

Outcome measures

Outcome measures
Measure	Advanced Malignancies Cohort n=239 Participants Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Number of Participants Experiencing Select Adverse Events Gastrointestinal Select AEs	57 Participants
Number of Participants Experiencing Select Adverse Events Hepatic Select AEs	33 Participants
Number of Participants Experiencing Select Adverse Events Pulmonary Select AEs	6 Participants
Number of Participants Experiencing Select Adverse Events Renal Select AEs	22 Participants
Number of Participants Experiencing Select Adverse Events Skin Select AEs	59 Participants
Number of Participants Experiencing Select Adverse Events Hypersensitivity/Infusion Reaction	7 Participants

SECONDARY outcome

Timeframe: From first dose to 30 days following the last dose (up to approximately 25 months)

Population: All treated participants

Number of participants who experienced AEs leading to dose delay or dose reduction. A dose will be considered as delayed if the delay is exceeding 3 days after the intended dose date (i.e., greater than or equal to 4 days from scheduled dosing date)

Outcome measures

Outcome measures
Measure	Advanced Malignancies Cohort n=239 Participants Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Number of Participants Experiencing Adverse Events (AEs) Leading to Dose Delay or Dose Reduction	61 Participants

SECONDARY outcome

Timeframe: From first dose to 30 days following the last dose (up to approximately 25 months)

Population: All treated participants with available measurements

Number of participants who experienced the laboratory abnormalities in specific liver tests described in the individual categories. ALT = Alanine Aminotransferase AST = Aspartate Aminotransferase ULN = Upper Limit of Normal

Outcome measures

Outcome measures
Measure	Advanced Malignancies Cohort n=231 Participants Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests ALT OR AST > 20XULN	1 Participants
Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests ALT OR AST > 3XULN	11 Participants
Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests ALT OR AST > 5XULN	8 Participants
Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests ALT OR AST > 10XULN	3 Participants
Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests TOTAL BILIRUBIN > 2XULN	5 Participants
Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests ALT OR AST > 3XULN + BILIRUBIN > 2XULN WITHIN 1 DAY	3 Participants
Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests ALT OR AST > 3XULN + BILIRUBIN > 2XULN WITHIN 30 DAYS	3 Participants

SECONDARY outcome

Timeframe: From first dose to 100 days following the last dose (up to approximately 27 months)

Population: All treated participants with available measurements

Number of participants who experienced the laboratory abnormalities in specific thyroid tests described in the individual categories. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal

Outcome measures

Outcome measures
Measure	Advanced Malignancies Cohort n=238 Participants Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH > ULN	62 Participants
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH > ULN WITH TSH <= ULN AT BASELINE	42 Participants
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH > ULN WITH AT LEAST ONE FT3/FT4 TEST VALUE < LLN	12 Participants
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH > ULN WITH ALL OTHER FT3/FT4 TEST VALUE >= LLN	0 Participants
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH > ULN WITH FT3/FT4 MISSING	2 Participants
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH < LLN	38 Participants
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH < LLN WITH TSH >= LLN AT BASELINE	25 Participants
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH < LLN WITH AT LEAST ONE FT3/FT4 TEST VALUE > ULN	8 Participants
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH < LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN	1 Participants
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH < LLN WITH FT3/FT4 TEST MISSING	1 Participants

Adverse Events

Advanced Malignancies Cohort

Serious events: 148 serious events

Other events: 216 other events

Deaths: 156 deaths

Serious adverse events

Serious adverse events
Measure	Advanced Malignancies Cohort n=239 participants at risk Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Blood and lymphatic system disorders Anaemia	1.3% 3/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Cardiac disorders Acute myocardial infarction	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Cardiac disorders Cardiac arrest	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Cardiac disorders Cardiac failure congestive	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Cardiac disorders Cardio-respiratory arrest	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Cardiac disorders Myocardial infarction	0.84% 2/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Cardiac disorders Supraventricular tachycardia	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Cardiac disorders Ventricular tachycardia	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Endocrine disorders Hyperthyroidism	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Endocrine disorders Hypophysitis	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Eye disorders Eye pain	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Eye disorders Eye swelling	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Abdominal pain	3.8% 9/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Abdominal pain lower	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Abdominal pain upper	0.84% 2/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Colitis	1.7% 4/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Diarrhoea	2.1% 5/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Diverticulum intestinal haemorrhagic	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Dysphagia	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Gastric haemorrhage	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Gastrointestinal haemorrhage	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Gastrointestinal oedema	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Ileus	0.84% 2/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Inguinal hernia	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Intestinal obstruction	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Nausea	1.7% 4/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Proctalgia	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Small intestinal obstruction	2.5% 6/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Subileus	0.84% 2/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Vomiting	1.7% 4/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Asthenia	0.84% 2/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Fatigue	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders General physical health deterioration	1.7% 4/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Localised oedema	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Non-cardiac chest pain	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Pain	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Peripheral swelling	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Pyrexia	0.84% 2/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Sudden death	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Hepatobiliary disorders Cholecystitis	1.3% 3/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Hepatobiliary disorders Hepatic lesion	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Immune system disorders Anaphylactic reaction	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Bacteraemia	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Bronchitis	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Cellulitis	1.3% 3/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Cholecystitis infective	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Device related infection	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Diarrhoea infectious	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Diverticulitis	0.84% 2/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Enterocolitis infectious	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Erysipelas	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Febrile infection	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Fungaemia	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Gastroenteritis	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Herpes zoster	0.84% 2/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Infectious pleural effusion	0.84% 2/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Intervertebral discitis	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Pelvic abscess	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Perinephric abscess	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Pharyngitis streptococcal	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Pneumonia	2.9% 7/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Renal abscess	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Sepsis	3.3% 8/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Septic shock	0.84% 2/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Skin infection	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Urinary tract infection	1.3% 3/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Urosepsis	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Injury, poisoning and procedural complications Humerus fracture	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Injury, poisoning and procedural complications Post procedural fever	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Investigations Blood creatinine increased	0.84% 2/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Investigations C-reactive protein increased	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Investigations Transaminases increased	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Metabolism and nutrition disorders Decreased appetite	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Metabolism and nutrition disorders Dehydration	2.1% 5/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Metabolism and nutrition disorders Diabetes mellitus	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Metabolism and nutrition disorders Hypokalaemia	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Metabolism and nutrition disorders Hypomagnesaemia	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Metabolism and nutrition disorders Hypovolaemia	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Metabolism and nutrition disorders Lactic acidosis	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Musculoskeletal and connective tissue disorders Arthralgia	0.84% 2/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Musculoskeletal and connective tissue disorders Back pain	1.3% 3/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Musculoskeletal and connective tissue disorders Flank pain	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Musculoskeletal and connective tissue disorders Myositis	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Musculoskeletal and connective tissue disorders Neck pain	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenoid cystic carcinoma	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Infected neoplasm	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm of cornea	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	24.3% 58/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mesothelioma	0.84% 2/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm progression	0.84% 2/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Penis carcinoma metastatic	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	1.7% 4/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Nervous system disorders Brain oedema	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Nervous system disorders Cerebellar infarction	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Nervous system disorders Cerebral infarction	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Nervous system disorders Cerebrovascular accident	0.84% 2/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Nervous system disorders Facial paralysis	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Nervous system disorders Headache	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Nervous system disorders Intracranial mass	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Nervous system disorders Neuritis cranial	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Nervous system disorders Spinal cord compression	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Psychiatric disorders Delirium	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Psychiatric disorders Mental status changes	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Renal and urinary disorders Acute kidney injury	1.7% 4/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Renal and urinary disorders Chronic kidney disease	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Renal and urinary disorders Haematuria	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Renal and urinary disorders Hydronephrosis	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Renal and urinary disorders Renal failure	0.84% 2/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Renal and urinary disorders Urinary tract obstruction	0.84% 2/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Reproductive system and breast disorders Vaginal haemorrhage	0.84% 2/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Reproductive system and breast disorders Vulvovaginal pain	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	1.3% 3/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Bronchostenosis	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.1% 5/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Hypoxia	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Laryngeal haemorrhage	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.7% 4/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Skin and subcutaneous tissue disorders Rash maculo-papular	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Vascular disorders Embolism	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Vascular disorders Venous stenosis	0.42% 1/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).

Other adverse events

Other adverse events
Measure	Advanced Malignancies Cohort n=239 participants at risk Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Blood and lymphatic system disorders Anaemia	17.2% 41/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Endocrine disorders Hypothyroidism	8.8% 21/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Abdominal pain	13.8% 33/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Abdominal pain upper	5.0% 12/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Constipation	20.9% 50/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Diarrhoea	21.8% 52/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Dry mouth	5.9% 14/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Nausea	22.2% 53/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Vomiting	13.4% 32/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Chills	5.9% 14/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Fatigue	37.7% 90/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Oedema peripheral	10.0% 24/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Pyrexia	10.0% 24/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Upper respiratory tract infection	7.1% 17/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Urinary tract infection	9.2% 22/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Investigations Alanine aminotransferase increased	6.7% 16/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Investigations Aspartate aminotransferase increased	7.5% 18/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Investigations Blood alkaline phosphatase increased	5.0% 12/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Investigations Blood creatinine increased	6.3% 15/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Investigations Weight decreased	9.2% 22/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Metabolism and nutrition disorders Decreased appetite	15.5% 37/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Metabolism and nutrition disorders Dehydration	9.6% 23/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Metabolism and nutrition disorders Hypokalaemia	7.5% 18/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Metabolism and nutrition disorders Hyponatraemia	6.3% 15/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Metabolism and nutrition disorders Hypophosphataemia	5.0% 12/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Musculoskeletal and connective tissue disorders Arthralgia	14.2% 34/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Musculoskeletal and connective tissue disorders Back pain	11.3% 27/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Musculoskeletal and connective tissue disorders Pain in extremity	6.3% 15/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Nervous system disorders Dizziness	6.3% 15/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Nervous system disorders Headache	7.9% 19/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Psychiatric disorders Anxiety	5.4% 13/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Psychiatric disorders Insomnia	7.5% 18/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Cough	18.0% 43/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Dyspnoea	18.4% 44/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Skin and subcutaneous tissue disorders Dry skin	5.0% 12/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Skin and subcutaneous tissue disorders Pruritus	10.9% 26/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Skin and subcutaneous tissue disorders Rash	8.4% 20/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Vascular disorders Hypertension	7.1% 17/239 • All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

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Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
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