Trial Outcomes & Findings for A Study of Nivolumab in Participants With Metastatic or Unresectable Bladder Cancer (NCT NCT02387996)

Last Updated: 2022-11-01

Results Overview

Objective Response Rate (ORR) was defined as the number of participants with a best overall response of confirmed Complete Response (CR) or Partial Response (PR) (per RECIST 1.1 criteria) divided by the number of all treated participants. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors. CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. BIRC= blinded independent review committee

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

270 participants

Primary outcome timeframe

From the date of first dose to the date of objectively documented progression or the date of subsequent therapy, whichever occurs first (assessed up to 14 months)

Results posted on

2022-11-01

Participant Flow

Participant milestones

Participant milestones
Measure	Nivolumab 3 mg/kg Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Overall Study STARTED	270
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	270

Reasons for withdrawal

Reasons for withdrawal
Measure	Nivolumab 3 mg/kg Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Overall Study Disease Progression	167
Overall Study Study Drug Toxicity	31
Overall Study Adverse Event Unrelated to Study Drug	39
Overall Study Participant Request to Discontinue Treatment	20
Overall Study Subject Withdrew Consent	5
Overall Study Lost to Follow-up	1
Overall Study Poor/Non-Compliance	1
Overall Study Other Reasons	5
Overall Study Death	1

Baseline Characteristics

A Study of Nivolumab in Participants With Metastatic or Unresectable Bladder Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nivolumab 3 mg/kg n=270 Participants Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Age, Continuous	65.0 Years STANDARD_DEVIATION 9.38 • n=5 Participants
Sex: Female, Male Female	59 Participants n=5 Participants
Sex: Female, Male Male	211 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	156 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	112 Participants n=5 Participants
Race/Ethnicity, Customized White	231 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	30 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	3 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the date of first dose to the date of objectively documented progression or the date of subsequent therapy, whichever occurs first (assessed up to 14 months)

Population: All treated participants. Treated participants from Japan enrolled after main enrollment period were excluded from primary efficacy analysis.

Outcome measures

Outcome measures
Measure	Nivolumab 3 mg/kg n=265 Participants Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Objective Response Rate Per BIRC Assessment	19.6 Percent of participants Interval 15.0 to 24.9

PRIMARY outcome

Timeframe: From the date of first dose to the date of objectively documented progression or the date of subsequent therapy, whichever occurs first (assessed up to 14 months)

Population: All treated participants. Treated participants from Japan enrolled after main enrollment period were excluded from primary efficacy analysis.

Outcome measures

Outcome measures
Measure	Nivolumab 3 mg/kg n=265 Participants Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
ORR Per BIRC Assessment by PD-L1 Expression Level PD-L1 <1%	16.1 Percent of Participants Interval 10.5 to 23.1
ORR Per BIRC Assessment by PD-L1 Expression Level PD-L1 >= 1%	23.8 Percent of Participants Interval 16.5 to 32.3
ORR Per BIRC Assessment by PD-L1 Expression Level PD-L1 <5%	15.8 Percent of Participants Interval 10.8 to 21.8
ORR Per BIRC Assessment by PD-L1 Expression Level PD-L1 >=5%	28.4 Percent of Participants Interval 18.9 to 39.5

PRIMARY outcome

Timeframe: From first dosing date to the date of the first confirmed response (up to approximately 14 months)

Population: All responders-includes responders who had neither progressed nor initiated subsequent therapy at the time of analysis, and excludes responders censored prior to 12 weeks of the clinical data cutoff date (if this cutoff date is before week 48) or prior to 18 weeks of the clinical data cutoff date (if this cutoff date is after or on week 48)

TTR is defined as the time from first dosing date to the date of the first confirmed complete response (CR) or partial response (PR), as assessed by the Blinded Independent Review Committee (BIRC). Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Nivolumab 3 mg/kg n=52 Participants Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Time to Response (TTR)	1.87 Months Interval 1.6 to 5.9

PRIMARY outcome

Timeframe: From the first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurs first (up to approximately 14 months)

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 using RECIST 1.1 criteria or death due to any cause, whichever occurs first. Participants who start subsequent therapy without a prior reported progression will be censored at the last evaluable tumor assessments prior to initiation of the subsequent anticancer therapy. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who neither progress nor die will be censored on the date of their last evaluable tumor assessment.

Outcome measures

Outcome measures
Measure	Nivolumab 3 mg/kg n=52 Participants Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Duration of Response (DOR)	NA Months Interval 7.43 to Median and upper limit not calculated due to insufficient number of events.

SECONDARY outcome

Timeframe: From first dosing date to the date of the first documented tumor progression (up to approximately 6 months)

Population: All treated participants

PFS was defined as the time from first dosing date to the date of the first documented tumor progression, based on Blinded Independent Review Committee (BIRC) assessments or death due to any cause. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. PD-L1 expression level is defined as membranous staining in greater than or equal to 5% and greater than or equal to 1% tumor cells.

Outcome measures

Outcome measures
Measure	Nivolumab 3 mg/kg n=270 Participants Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Progression Free Survival (PFS) All treated participants	1.94 Months Interval 1.87 to 2.33
Progression Free Survival (PFS) PD-L1 <1%	1.87 Months Interval 1.74 to 2.0
Progression Free Survival (PFS) PD-L1 >= 1%	3.45 Months Interval 1.91 to 3.71
Progression Free Survival (PFS) PD-L1 <5%	1.87 Months Interval 1.81 to 2.04
Progression Free Survival (PFS) PD-L1 >=5%	3.68 Months Interval 1.91 to 5.52

SECONDARY outcome

Timeframe: From first dosing date to the date of death (up to approximately 23 months)

Population: All treated participants

Overall Survival was defined as the time from first dosing date to the date of death. A participant who had not died was censored at last known date alive. PD-L1 expression level = membranous staining in greater than or equal to 5% and greater than or equal to 1% tumor cells.

Outcome measures

Outcome measures
Measure	Nivolumab 3 mg/kg n=270 Participants Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Overall Survival (OS) All treated participants	8.57 Months Interval 6.05 to 11.27
Overall Survival (OS) PD-L1 <1%	5.95 Months Interval 4.37 to 8.08
Overall Survival (OS) PD-L1 >= 1%	11.86 Months Interval 9.1 to 19.12
Overall Survival (OS) PD-L1 <5%	6.24 Months Interval 4.96 to 9.0
Overall Survival (OS) PD-L1 >=5%	13.54 Months Interval 9.63 to 22.14

SECONDARY outcome

Timeframe: From the date of first dose to the date of objectively documented progression or the date of subsequent therapy, whichever occurs first (up to approximately 45 months)

Population: All treated participants

Investigator-assessed ORR was defined as the percent of participants with a best overall response of confirmed complete response (CR) or partial response (PR). Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD-L1 expression level = Membranous staining in greater than or equal to 5% and greater than or equal to 1% tumor cells.

Outcome measures

Outcome measures
Measure	Nivolumab 3 mg/kg n=270 Participants Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Objective Response Rate (ORR) Per Investigator All treated participants	24.8 Percent of Participants Interval 19.8 to 30.4
Objective Response Rate (ORR) Per Investigator PD-L1 <1%	19.9 Percent of Participants Interval 13.7 to 27.3
Objective Response Rate (ORR) Per Investigator PD-L1 >= 1%	30.6 Percent of Participants Interval 22.7 to 39.6
Objective Response Rate (ORR) Per Investigator PD-L1 <5%	20.9 Percent of Participants Interval 15.3 to 27.4
Objective Response Rate (ORR) Per Investigator PD-L1 >=5%	33.7 Percent of Participants Interval 23.7 to 44.9

POST_HOC outcome

Timeframe: From first dosing date to the date of the first confirmed response (up to approximately 14 months)

Outcome measures

Outcome measures
Measure	Nivolumab 3 mg/kg n=56 Participants Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Time to Response (TTR) - Extended Collection	1.97 Months Interval 1.6 to 13.8

POST_HOC outcome

Timeframe: From the first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurs first (up to approximately 32 months)

DOR is the time from first confirmed response, complete (CR) or partial response (PR) to the date of the first tumor progression PER RECIST 1.1 criteria or death due to any cause, whichever occurs first. Participants without prior reported progression will be censored at the last evaluable tumor assessments prior to subsequent anticancer therapy. Participants who die without a reported prior progression will be considered on the date of their death. Participants who neither progress nor die will be censored on the date of their last evaluable tumor assessment. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions. Note: This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date.

Outcome measures

Outcome measures
Measure	Nivolumab 3 mg/kg n=56 Participants Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Duration of Response (DOR) - Extended Collection	20.27 Months Interval 11.5 to 31.31

POST_HOC outcome

Timeframe: From the date of first dose to the date of objectively documented progression or the date of subsequent therapy, whichever occurs first (up approximately to 43 months)

Population: All treated participants

Objective Response Rate (ORR) was defined as the percent of participants with a best overall response of confirmed Complete Response (CR) or Partial Response (PR) (per RECIST 1.1 criteria). RECIST 1.1 = Response Evaluation Criteria in Solid Tumors. CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. BIRC= blinded independent review committee PD-L1 expression level= membranous staining in greater than or equal to 5% and greater than or equal to 1% tumor cells. Note: This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date."

Outcome measures

Outcome measures
Measure	Nivolumab 3 mg/kg n=270 Participants Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Objective Response Rate (ORR) Per BIRC Assessment - Extended Collection All treated participants	20.7 Percent of Participants Interval 16.1 to 26.1
Objective Response Rate (ORR) Per BIRC Assessment - Extended Collection PD-L1 <1%	16.4 Percent of Participants Interval 10.8 to 23.5
Objective Response Rate (ORR) Per BIRC Assessment - Extended Collection PD-L1 >= 1%	25.8 Percent of Participants Interval 18.4 to 34.4
Objective Response Rate (ORR) Per BIRC Assessment - Extended Collection PD-L1 <5%	16.0 Percent of Participants Interval 11.1 to 22.1
Objective Response Rate (ORR) Per BIRC Assessment - Extended Collection PD-L1 >=5%	31.3 Percent of Participants Interval 21.6 to 42.4

Adverse Events

Nivolumab 3 mg/kg

Serious events: 199 serious events

Other events: 245 other events

Deaths: 225 deaths

Serious adverse events

Serious adverse events
Measure	Nivolumab 3 mg/kg n=270 participants at risk Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Blood and lymphatic system disorders Agranulocytosis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Blood and lymphatic system disorders Anaemia	1.1% 3/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Blood and lymphatic system disorders Lymphadenopathy	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Blood and lymphatic system disorders Thrombocytopenia	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Cardiac disorders Acute coronary syndrome	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Cardiac disorders Acute myocardial infarction	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Cardiac disorders Aortic valve stenosis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Cardiac disorders Atrial fibrillation	1.1% 3/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Cardiac disorders Atrial flutter	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Cardiac disorders Cardiac arrest	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Cardiac disorders Cardio-respiratory arrest	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Cardiac disorders Cardiovascular disorder	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Cardiac disorders Hypertensive heart disease	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Cardiac disorders Pericarditis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Cardiac disorders Tachycardia	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Endocrine disorders Adrenal insufficiency	1.1% 3/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Endocrine disorders Hypophysitis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Eye disorders Uveitis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Abdominal pain	1.5% 4/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Abdominal pain upper	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Autoimmune colitis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Colitis	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Constipation	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Diarrhoea	2.6% 7/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Duodenitis	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Enteritis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Gastritis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Gastrointestinal haemorrhage	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Haematemesis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Ileus	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Immune-mediated enterocolitis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Inguinal hernia	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Intestinal obstruction	1.5% 4/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Intestinal perforation	1.1% 3/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Large intestinal obstruction	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Nausea	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Pancreatitis	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Rectal haemorrhage	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Small intestinal obstruction	2.6% 7/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Vomiting	1.5% 4/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
General disorders Asthenia	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
General disorders Disease progression	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
General disorders Fatigue	1.1% 3/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
General disorders General physical health deterioration	4.4% 12/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
General disorders Malaise	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
General disorders Mass	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
General disorders Multiple organ dysfunction syndrome	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
General disorders Non-cardiac chest pain	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
General disorders Obstruction	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
General disorders Oedema peripheral	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
General disorders Pain	1.9% 5/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
General disorders Pelvic mass	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
General disorders Pyrexia	1.5% 4/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
General disorders Sudden death	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
General disorders Systemic inflammatory response syndrome	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Hepatobiliary disorders Biliary obstruction	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Hepatobiliary disorders Cholecystitis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Hepatobiliary disorders Hepatic failure	1.1% 3/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Anal abscess	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Arthritis infective	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Bacteraemia	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Bacterial infection	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Bronchiolitis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Bronchitis	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Candida infection	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Cellulitis	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Clostridium difficile infection	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Coronavirus infection	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Endocarditis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Erysipelas	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Escherichia urinary tract infection	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Infected lymphocele	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Kidney infection	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Pneumonia	2.2% 6/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Pyelonephritis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Sepsis	4.4% 12/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Septic shock	1.5% 4/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Staphylococcal infection	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Stoma site cellulitis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Upper respiratory tract infection	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Urinary tract infection	6.3% 17/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Urosepsis	1.1% 3/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Injury, poisoning and procedural complications Femur fracture	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Injury, poisoning and procedural complications Hip fracture	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Injury, poisoning and procedural complications Infusion related reaction	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Injury, poisoning and procedural complications Pelvic fracture	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Injury, poisoning and procedural complications Toxicity to various agents	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Investigations Blood bilirubin increased	1.1% 3/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Investigations Hepatic enzyme increased	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Investigations Influenza A virus test positive	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Investigations Lipase increased	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Investigations Liver function test increased	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Investigations Platelet count decreased	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Investigations Quality of life decreased	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Investigations Transaminases increased	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Metabolism and nutrition disorders Decreased appetite	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Metabolism and nutrition disorders Dehydration	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Metabolism and nutrition disorders Failure to thrive	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Metabolism and nutrition disorders Hypercalcaemia	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Metabolism and nutrition disorders Hyperglycaemia	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Metabolism and nutrition disorders Hyperkalaemia	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Metabolism and nutrition disorders Hypervolaemia	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Metabolism and nutrition disorders Hyponatraemia	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Metabolism and nutrition disorders Metabolic acidosis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Musculoskeletal and connective tissue disorders Back pain	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Musculoskeletal and connective tissue disorders Synovitis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma pancreas	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder neoplasm	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	1.5% 4/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	35.2% 95/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	1.5% 4/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lung	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell cancer of renal pelvis and ureter metastatic	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma recurrent	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour associated fever	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Nervous system disorders Brain oedema	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Nervous system disorders Cerebellar haematoma	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Nervous system disorders Cerebral disorder	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Nervous system disorders Cerebral infarction	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Nervous system disorders Cerebrovascular accident	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Nervous system disorders Epilepsy	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Nervous system disorders Monoplegia	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Nervous system disorders Paraesthesia	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Nervous system disorders Presyncope	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Nervous system disorders Spinal cord compression	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Nervous system disorders Syncope	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Product Issues Device dislocation	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Product Issues Thrombosis in device	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Psychiatric disorders Anxiety	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Renal and urinary disorders Acute kidney injury	1.1% 3/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Renal and urinary disorders Bladder tamponade	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Renal and urinary disorders Haematuria	1.5% 4/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Renal and urinary disorders Hydronephrosis	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Renal and urinary disorders Nephrolithiasis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Renal and urinary disorders Renal failure	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Renal and urinary disorders Renal impairment	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Renal and urinary disorders Urinary tract obstruction	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.9% 5/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.6% 7/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.1% 3/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.5% 4/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Skin and subcutaneous tissue disorders Pemphigoid	0.74% 2/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Skin and subcutaneous tissue disorders Rash pruritic	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Vascular disorders Arteriosclerosis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Vascular disorders Arteriovenous fistula	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Vascular disorders Circulatory collapse	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Vascular disorders Deep vein thrombosis	1.5% 4/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Vascular disorders Hypertension	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Vascular disorders Hypotension	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Vascular disorders Shock haemorrhagic	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Vascular disorders Superior vena cava syndrome	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Vascular disorders Thrombosis	0.37% 1/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).

Other adverse events

Other adverse events
Measure	Nivolumab 3 mg/kg n=270 participants at risk Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Blood and lymphatic system disorders Anaemia	21.5% 58/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Endocrine disorders Hypothyroidism	11.9% 32/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Abdominal pain	12.6% 34/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Constipation	22.2% 60/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Diarrhoea	22.2% 60/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Nausea	26.3% 71/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Gastrointestinal disorders Vomiting	15.6% 42/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
General disorders Asthenia	15.9% 43/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
General disorders Chills	8.1% 22/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
General disorders Fatigue	35.9% 97/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
General disorders Oedema peripheral	16.7% 45/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
General disorders Pyrexia	24.1% 65/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Nasopharyngitis	5.9% 16/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Upper respiratory tract infection	7.4% 20/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Infections and infestations Urinary tract infection	15.9% 43/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Investigations Amylase increased	7.4% 20/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Investigations Blood alkaline phosphatase increased	5.2% 14/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Investigations Blood creatinine increased	8.9% 24/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Investigations Lipase increased	6.7% 18/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Investigations Weight decreased	8.9% 24/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Metabolism and nutrition disorders Decreased appetite	27.4% 74/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Metabolism and nutrition disorders Dehydration	7.8% 21/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Metabolism and nutrition disorders Hyperglycaemia	5.9% 16/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Metabolism and nutrition disorders Hypokalaemia	5.6% 15/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Metabolism and nutrition disorders Hyponatraemia	7.0% 19/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Musculoskeletal and connective tissue disorders Arthralgia	14.8% 40/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Musculoskeletal and connective tissue disorders Back pain	15.2% 41/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Musculoskeletal and connective tissue disorders Bone pain	5.2% 14/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Musculoskeletal and connective tissue disorders Myalgia	7.4% 20/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Musculoskeletal and connective tissue disorders Pain in extremity	9.3% 25/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Nervous system disorders Dizziness	7.8% 21/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Nervous system disorders Headache	7.4% 20/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Nervous system disorders Paraesthesia	5.2% 14/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Psychiatric disorders Anxiety	6.3% 17/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Psychiatric disorders Insomnia	10.7% 29/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Renal and urinary disorders Haematuria	8.1% 22/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Respiratory, thoracic and mediastinal disorders Cough	21.9% 59/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Respiratory, thoracic and mediastinal disorders Dyspnoea	16.7% 45/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Respiratory, thoracic and mediastinal disorders Pneumonitis	5.6% 15/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Skin and subcutaneous tissue disorders Dry skin	5.9% 16/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Skin and subcutaneous tissue disorders Pruritus	16.7% 45/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Skin and subcutaneous tissue disorders Rash	17.0% 46/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).
Vascular disorders Hypotension	6.3% 17/270 • Participants were assessed for all-cause mortality from their first dose to study completion, (up to approximately 80 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 78 months).

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Email: [email protected]

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.
Publication restrictions are in place

Restriction type: OTHER