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

• ClinicalTrials.gov Identifier: NCT02387996
• Recruitment Status: Completed
• First Posted: March 13, 2015
• Results First Posted: May 24, 2017
• Last Update Posted: November 1, 2022
• Sponsor: Bristol-Myers Squibb
• Collaborator: Ono Pharmaceutical Co. Ltd
• Information provided by (Responsible Party): Bristol-Myers Squibb

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Various Advanced Cancer
• Intervention: Drug: Nivolumab
• Enrollment: 270

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Nivolumab 3 mg/kg
Arm/Group Description	Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Period Title: Overall Study
Started	270
Completed [1]	0
Not Completed	270
Reason Not Completed
Disease Progression	167
Study Drug Toxicity	31
Adverse Event Unrelated to Study Drug	39
Participant Request to Discontinue Treatment	20
Subject Withdrew Consent	5
Lost to Follow-up	1
Poor/Non-Compliance	1
Other Reasons	5
Death	1
[1] Completed=continuing in the study treatment

Baseline Characteristics

Arm/Group Title		Nivolumab 3 mg/kg
Arm/Group Description		Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Overall Number of Baseline Participants		270
Baseline Analysis Population Description		All Treated Participants
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	270 participants
		65.0 (9.38)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	270 participants
	Female	59 21.9%
	Male	211 78.1%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	270 participants
	Hispanic or Latino	2 0.7%
	Not Hispanic or Latino	156 57.8%
	Unknown or Not Reported	112 41.5%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	270 participants
	White	231 85.6%
	Black or African American	2 0.7%
	Asian	30 11.1%
	American Indian or Alaska Native	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Other	3 1.1%
	Not Reported	4 1.5%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate Per BIRC Assessment
Description	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
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Nivolumab 3 mg/kg
Arm/Group Description:	Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Overall Number of Participants Analyzed	265
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percent of participants
	19.6; (15.0 to 24.9)

2. Primary Outcome

Title	ORR Per BIRC Assessment by PD-L1 Expression Level
Description	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 PD-L1 expression level= membranous staining in greater than or equal to 5% and greater than or equal to 1% tumor cells. n = Number of participants in each category
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Nivolumab 3 mg/kg
Arm/Group Description:	Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Overall Number of Participants Analyzed	265
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percent of Participants
PD-L1 <1%	16.1; (10.5 to 23.1)
PD-L1 >= 1%	23.8; (16.5 to 32.3)
PD-L1 <5%	15.8; (10.8 to 21.8)
PD-L1 >=5%	28.4; (18.9 to 39.5)

3. Primary Outcome

Title	Time to Response (TTR)
Description	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.
Time Frame	From first dosing date to the date of the first confirmed response (up to approximately 14 months)

Outcome Measure Data

Analysis Population Description

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)

Arm/Group Title	Nivolumab 3 mg/kg
Arm/Group Description:	Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Overall Number of Participants Analyzed	52
Median (Full Range); Unit of Measure: Months
	1.87; (1.6 to 5.9)

4. Primary Outcome

Title	Duration of Response (DOR)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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)

Arm/Group Title	Nivolumab 3 mg/kg
Arm/Group Description:	Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Overall Number of Participants Analyzed	52
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (7.43 to NA)

[1]

Median and upper limit not calculated due to insufficient number of events.

5. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	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.
Time Frame	From first dosing date to the date of the first documented tumor progression (up to approximately 6 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title		Nivolumab 3 mg/kg
Arm/Group Description:		Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Overall Number of Participants Analyzed		270
Median (95% Confidence Interval); Unit of Measure: Months
All treated participants	Number Analyzed	270 participants
		1.94; (1.87 to 2.33)
PD-L1 <1%	Number Analyzed	146 participants
		1.87; (1.74 to 2.00)
PD-L1 >= 1%	Number Analyzed	124 participants
		3.45; (1.91 to 3.71)
PD-L1 <5%	Number Analyzed	187 participants
		1.87; (1.81 to 2.04)
PD-L1 >=5%	Number Analyzed	83 participants
		3.68; (1.91 to 5.52)

6. Secondary Outcome

Title	Overall Survival (OS)
Description	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.
Time Frame	From first dosing date to the date of death (up to approximately 23 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title		Nivolumab 3 mg/kg
Arm/Group Description:		Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Overall Number of Participants Analyzed		270
Median (95% Confidence Interval); Unit of Measure: Months
All treated participants	Number Analyzed	270 participants
		8.57; (6.05 to 11.27)
PD-L1 <1%	Number Analyzed	146 participants
		5.95; (4.37 to 8.08)
PD-L1 >= 1%	Number Analyzed	124 participants
		11.86; (9.10 to 19.12)
PD-L1 <5%	Number Analyzed	187 participants
		6.24; (4.96 to 9.00)
PD-L1 >=5%	Number Analyzed	83 participants
		13.54; (9.63 to 22.14)

7. Secondary Outcome

Title	Objective Response Rate (ORR) Per Investigator
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title		Nivolumab 3 mg/kg
Arm/Group Description:		Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Overall Number of Participants Analyzed		270
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percent of Participants
All treated participants	Number Analyzed	270 participants
		24.8; (19.8 to 30.4)
PD-L1 <1%	Number Analyzed	146 participants
		19.9; (13.7 to 27.3)
PD-L1 >= 1%	Number Analyzed	124 participants
		30.6; (22.7 to 39.6)
PD-L1 <5%	Number Analyzed	187 participants
		20.9; (15.3 to 27.4)
PD-L1 >=5%	Number Analyzed	83 participants
		33.7; (23.7 to 44.9)

8. Post-Hoc Outcome

Title	Time to Response (TTR) - Extended Collection
Description	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. 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.
Time Frame	From first dosing date to the date of the first confirmed response (up to approximately 14 months)

Outcome Measure Data

Analysis Population Description

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)

Arm/Group Title	Nivolumab 3 mg/kg
Arm/Group Description:	Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Overall Number of Participants Analyzed	56
Median (Full Range); Unit of Measure: Months
	1.97; (1.6 to 13.8)

9. Post-Hoc Outcome

Title	Duration of Response (DOR) - Extended Collection
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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)

Arm/Group Title	Nivolumab 3 mg/kg
Arm/Group Description:	Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Overall Number of Participants Analyzed	56
Median (95% Confidence Interval); Unit of Measure: Months
	20.27; (11.50 to 31.31)

10. Post-Hoc Outcome

Title	Objective Response Rate (ORR) Per BIRC Assessment - Extended Collection
Description	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."
Time Frame	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)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title		Nivolumab 3 mg/kg
Arm/Group Description:		Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
Overall Number of Participants Analyzed		270
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percent of Participants
All treated participants	Number Analyzed	270 participants
		20.7; (16.1 to 26.1)
PD-L1 <1%	Number Analyzed	146 participants
		16.4; (10.8 to 23.5)
PD-L1 >= 1%	Number Analyzed	124 participants
		25.8; (18.4 to 34.4)
PD-L1 <5%	Number Analyzed	187 participants
		16.0; (11.1 to 22.1)
PD-L1 >=5%	Number Analyzed	83 participants
		31.3; (21.6 to 42.4)

Adverse Events

Time Frame	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).
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Nivolumab 3 mg/kg
Arm/Group Description	Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W
All-Cause Mortality
	Nivolumab 3 mg/kg
	Affected / at Risk (%)
Total	225/270 (83.33%)
Serious Adverse Events
	Nivolumab 3 mg/kg
	Affected / at Risk (%)
Total	199/270 (73.70%)
Blood and lymphatic system disorders
Agranulocytosis † 1	1/270 (0.37%)
Anaemia † 1	3/270 (1.11%)
Lymphadenopathy † 1	1/270 (0.37%)
Thrombocytopenia † 1	2/270 (0.74%)
Cardiac disorders
Acute coronary syndrome † 1	1/270 (0.37%)
Acute myocardial infarction † 1	1/270 (0.37%)
Aortic valve stenosis † 1	1/270 (0.37%)
Atrial fibrillation † 1	3/270 (1.11%)
Atrial flutter † 1	1/270 (0.37%)
Cardiac arrest † 1	1/270 (0.37%)
Cardio-respiratory arrest † 1	1/270 (0.37%)
Cardiovascular disorder † 1	1/270 (0.37%)
Hypertensive heart disease † 1	1/270 (0.37%)
Pericarditis † 1	1/270 (0.37%)
Tachycardia † 1	1/270 (0.37%)
Endocrine disorders
Adrenal insufficiency † 1	3/270 (1.11%)
Hypophysitis † 1	1/270 (0.37%)
Eye disorders
Uveitis † 1	1/270 (0.37%)
Gastrointestinal disorders
Abdominal pain † 1	4/270 (1.48%)
Abdominal pain upper † 1	1/270 (0.37%)
Autoimmune colitis † 1	1/270 (0.37%)
Colitis † 1	2/270 (0.74%)
Constipation † 1	2/270 (0.74%)
Diarrhoea † 1	7/270 (2.59%)
Duodenal ulcer haemorrhage † 1	2/270 (0.74%)
Duodenitis † 1	2/270 (0.74%)
Enteritis † 1	1/270 (0.37%)
Gastritis † 1	1/270 (0.37%)
Gastrointestinal haemorrhage † 1	1/270 (0.37%)
Haematemesis † 1	1/270 (0.37%)
Ileus † 1	2/270 (0.74%)
Immune-mediated enterocolitis † 1	1/270 (0.37%)
Inguinal hernia † 1	1/270 (0.37%)
Intestinal obstruction † 1	4/270 (1.48%)
Intestinal perforation † 1	3/270 (1.11%)
Large intestinal obstruction † 1	1/270 (0.37%)
Nausea † 1	2/270 (0.74%)
Pancreatitis † 1	2/270 (0.74%)
Rectal haemorrhage † 1	2/270 (0.74%)
Small intestinal obstruction † 1	7/270 (2.59%)
Vomiting † 1	4/270 (1.48%)
General disorders
Asthenia † 1	2/270 (0.74%)
Disease progression † 1	1/270 (0.37%)
Fatigue † 1	3/270 (1.11%)
General physical health deterioration † 1	12/270 (4.44%)
Malaise † 1	2/270 (0.74%)
Mass † 1	1/270 (0.37%)
Multiple organ dysfunction syndrome † 1	1/270 (0.37%)
Non-cardiac chest pain † 1	2/270 (0.74%)
Obstruction † 1	1/270 (0.37%)
Oedema peripheral † 1	2/270 (0.74%)
Pain † 1	5/270 (1.85%)
Pelvic mass † 1	1/270 (0.37%)
Pyrexia † 1	4/270 (1.48%)
Sudden death † 1	1/270 (0.37%)
Systemic inflammatory response syndrome † 1	1/270 (0.37%)
Hepatobiliary disorders
Biliary obstruction † 1	1/270 (0.37%)
Cholecystitis † 1	1/270 (0.37%)
Hepatic failure † 1	3/270 (1.11%)
Infections and infestations
Anal abscess † 1	1/270 (0.37%)
Arthritis infective † 1	1/270 (0.37%)
Bacteraemia † 1	1/270 (0.37%)
Bacterial infection † 1	1/270 (0.37%)
Bronchiolitis † 1	1/270 (0.37%)
Bronchitis † 1	2/270 (0.74%)
Candida infection † 1	1/270 (0.37%)
Cellulitis † 1	2/270 (0.74%)
Clostridium difficile infection † 1	1/270 (0.37%)
Coronavirus infection † 1	1/270 (0.37%)
Endocarditis † 1	1/270 (0.37%)
Erysipelas † 1	1/270 (0.37%)
Escherichia urinary tract infection † 1	1/270 (0.37%)
Infected lymphocele † 1	1/270 (0.37%)
Kidney infection † 1	1/270 (0.37%)
Pneumonia † 1	6/270 (2.22%)
Pyelonephritis † 1	1/270 (0.37%)
Sepsis † 1	12/270 (4.44%)
Septic shock † 1	4/270 (1.48%)
Staphylococcal infection † 1	1/270 (0.37%)
Stoma site cellulitis † 1	1/270 (0.37%)
Upper respiratory tract infection † 1	1/270 (0.37%)
Urinary tract infection † 1	17/270 (6.30%)
Urosepsis † 1	3/270 (1.11%)
Injury, poisoning and procedural complications
Femur fracture † 1	1/270 (0.37%)
Hip fracture † 1	1/270 (0.37%)
Infusion related reaction † 1	1/270 (0.37%)
Lumbar vertebral fracture † 1	1/270 (0.37%)
Pelvic fracture † 1	1/270 (0.37%)
Toxicity to various agents † 1	1/270 (0.37%)
Investigations
Blood bilirubin increased † 1	3/270 (1.11%)
Hepatic enzyme increased † 1	1/270 (0.37%)
Influenza A virus test positive † 1	1/270 (0.37%)
Lipase increased † 1	1/270 (0.37%)
Liver function test increased † 1	1/270 (0.37%)
Platelet count decreased † 1	1/270 (0.37%)
Quality of life decreased † 1	1/270 (0.37%)
Transaminases increased † 1	1/270 (0.37%)
Metabolism and nutrition disorders
Decreased appetite † 1	2/270 (0.74%)
Dehydration † 1	2/270 (0.74%)
Failure to thrive † 1	1/270 (0.37%)
Hypercalcaemia † 1	2/270 (0.74%)
Hyperglycaemia † 1	1/270 (0.37%)
Hyperkalaemia † 1	1/270 (0.37%)
Hypervolaemia † 1	1/270 (0.37%)
Hyponatraemia † 1	1/270 (0.37%)
Metabolic acidosis † 1	1/270 (0.37%)
Musculoskeletal and connective tissue disorders
Back pain † 1	2/270 (0.74%)
Synovitis † 1	1/270 (0.37%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas † 1	1/270 (0.37%)
Bladder neoplasm † 1	1/270 (0.37%)
Cancer pain † 1	4/270 (1.48%)
Malignant neoplasm progression † 1	95/270 (35.19%)
Metastases to bone † 1	1/270 (0.37%)
Metastases to central nervous system † 1	4/270 (1.48%)
Metastases to lung † 1	1/270 (0.37%)
Squamous cell carcinoma † 1	1/270 (0.37%)
Transitional cell cancer of renal pelvis and ureter metastatic † 1	2/270 (0.74%)
Transitional cell carcinoma † 1	2/270 (0.74%)
Transitional cell carcinoma recurrent † 1	1/270 (0.37%)
Tumour associated fever † 1	1/270 (0.37%)
Tumour pain † 1	2/270 (0.74%)
Nervous system disorders
Brain oedema † 1	2/270 (0.74%)
Cerebellar haematoma † 1	1/270 (0.37%)
Cerebral disorder † 1	1/270 (0.37%)
Cerebral infarction † 1	1/270 (0.37%)
Cerebrovascular accident † 1	2/270 (0.74%)
Epilepsy † 1	2/270 (0.74%)
Monoplegia † 1	1/270 (0.37%)
Paraesthesia † 1	2/270 (0.74%)
Presyncope † 1	1/270 (0.37%)
Spinal cord compression † 1	1/270 (0.37%)
Syncope † 1	1/270 (0.37%)
Product Issues
Device dislocation † 1	1/270 (0.37%)
Thrombosis in device † 1	1/270 (0.37%)
Psychiatric disorders
Anxiety † 1	1/270 (0.37%)
Renal and urinary disorders
Acute kidney injury † 1	3/270 (1.11%)
Bladder tamponade † 1	2/270 (0.74%)
Haematuria † 1	4/270 (1.48%)
Hydronephrosis † 1	2/270 (0.74%)
Nephrolithiasis † 1	1/270 (0.37%)
Renal failure † 1	2/270 (0.74%)
Renal impairment † 1	1/270 (0.37%)
Urinary tract obstruction † 1	2/270 (0.74%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	2/270 (0.74%)
Dyspnoea † 1	5/270 (1.85%)
Haemoptysis † 1	1/270 (0.37%)
Interstitial lung disease † 1	1/270 (0.37%)
Pleural effusion † 1	2/270 (0.74%)
Pneumonitis † 1	7/270 (2.59%)
Pulmonary embolism † 1	3/270 (1.11%)
Respiratory distress † 1	1/270 (0.37%)
Respiratory failure † 1	4/270 (1.48%)
Skin and subcutaneous tissue disorders
Pemphigoid † 1	2/270 (0.74%)
Rash pruritic † 1	1/270 (0.37%)
Vascular disorders
Arteriosclerosis † 1	1/270 (0.37%)
Arteriovenous fistula † 1	1/270 (0.37%)
Circulatory collapse † 1	1/270 (0.37%)
Deep vein thrombosis † 1	4/270 (1.48%)
Hypertension † 1	1/270 (0.37%)
Hypotension † 1	1/270 (0.37%)
Shock haemorrhagic † 1	1/270 (0.37%)
Superior vena cava syndrome † 1	1/270 (0.37%)
Thrombosis † 1	1/270 (0.37%)
1 Term from vocabulary, 24.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Nivolumab 3 mg/kg
	Affected / at Risk (%)
Total	245/270 (90.74%)
Blood and lymphatic system disorders
Anaemia † 1	58/270 (21.48%)
Endocrine disorders
Hypothyroidism † 1	32/270 (11.85%)
Gastrointestinal disorders
Abdominal pain † 1	34/270 (12.59%)
Constipation † 1	60/270 (22.22%)
Diarrhoea † 1	60/270 (22.22%)
Nausea † 1	71/270 (26.30%)
Vomiting † 1	42/270 (15.56%)
General disorders
Asthenia † 1	43/270 (15.93%)
Chills † 1	22/270 (8.15%)
Fatigue † 1	97/270 (35.93%)
Oedema peripheral † 1	45/270 (16.67%)
Pyrexia † 1	65/270 (24.07%)
Infections and infestations
Nasopharyngitis † 1	16/270 (5.93%)
Upper respiratory tract infection † 1	20/270 (7.41%)
Urinary tract infection † 1	43/270 (15.93%)
Investigations
Amylase increased † 1	20/270 (7.41%)
Blood alkaline phosphatase increased † 1	14/270 (5.19%)
Blood creatinine increased † 1	24/270 (8.89%)
Lipase increased † 1	18/270 (6.67%)
Weight decreased † 1	24/270 (8.89%)
Metabolism and nutrition disorders
Decreased appetite † 1	74/270 (27.41%)
Dehydration † 1	21/270 (7.78%)
Hyperglycaemia † 1	16/270 (5.93%)
Hypokalaemia † 1	15/270 (5.56%)
Hyponatraemia † 1	19/270 (7.04%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	40/270 (14.81%)
Back pain † 1	41/270 (15.19%)
Bone pain † 1	14/270 (5.19%)
Myalgia † 1	20/270 (7.41%)
Pain in extremity † 1	25/270 (9.26%)
Nervous system disorders
Dizziness † 1	21/270 (7.78%)
Headache † 1	20/270 (7.41%)
Paraesthesia † 1	14/270 (5.19%)
Psychiatric disorders
Anxiety † 1	17/270 (6.30%)
Insomnia † 1	29/270 (10.74%)
Renal and urinary disorders
Haematuria † 1	22/270 (8.15%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	59/270 (21.85%)
Dyspnoea † 1	45/270 (16.67%)
Pneumonitis † 1	15/270 (5.56%)
Skin and subcutaneous tissue disorders
Dry skin † 1	16/270 (5.93%)
Pruritus † 1	45/270 (16.67%)
Rash † 1	46/270 (17.04%)
Vascular disorders
Hypotension † 1	17/270 (6.30%)
1 Term from vocabulary, 24.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb
• Phone: Please email
• EMail: Clinical.Trials@bms.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sharma P, Retz M, Siefker-Radtke A, Baron A, Necchi A, Bedke J, Plimack ER, Vaena D, Grimm MO, Bracarda S, Arranz JA, Pal S, Ohyama C, Saci A, Qu X, Lambert A, Krishnan S, Azrilevich A, Galsky MD. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017 Mar;18(3):312-322. doi: 10.1016/S1470-2045(17)30065-7. Epub 2017 Jan 26.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02387996
• Other Study ID Numbers: CA209-275
• First Submitted: February 26, 2015
• First Posted: March 13, 2015
• Results First Submitted: April 13, 2017
• Results First Posted: May 24, 2017
• Last Update Posted: November 1, 2022