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A Study to Compare BMS-936558 to the Physician's Choice of Either Dacarbazine or Carboplatin and Paclitaxel in Advanced Melanoma Patients That Have Progressed Following Anti-CTLA-4 Therapy (CheckMate 037)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01721746
Recruitment Status : Active, not recruiting
First Posted : November 6, 2012
Results First Posted : March 22, 2017
Last Update Posted : May 18, 2020
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Unresectable or Metastatic Melanoma
Interventions Biological: BMS-936558
Drug: Dacarbazine
Drug: Carboplatin
Drug: Paclitaxel
Enrollment 631
Recruitment Details 631 enrolled. 405 randomized. Reasons not randomized: 1 adverse event, 17 withdrew consent, 3 deaths, 1 lost to follow-up, 1 poor/non compliance, 200 no longer met study criteria, 3 unspecified. 370 treated. Reasons not treated: 13 request to discontinue study treatment, 17 withdrew consent, 1 poor/non compliance, 4 no longer met study criteria.
Pre-assignment Details  
Arm/Group Title Nivolumab 3 mg/kg (IV) Investigator's Choice (Dacarbazine) Investigator's Choice (Carboplatin+Paclitaxel)
Hide Arm/Group Description Nivolumab 3 mg/kg solution for injection by intravenous (IV), every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Dacarbazine: 1000mg/m2, Powder for IV solution, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Carboplatin: Area under the concentration-time curve (AUC) 6, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Paclitaxel: 175 mg/ m2, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Period Title: Treatment Period
Started 268 45 57
Completed 35 [1] 0 0
Not Completed 233 45 57
Reason Not Completed
Disease Progression             182             40             34
Study Drug Toxicity             15             2             9
Adverse Event Unrelated to Study Drug             6             1             2
Subject Request to Discontinue Treatment             19             1             6
Subject Withdrew Consent             3             0             2
Maximum Clinical Benefit             1             0             3
Poor/Non-compliance             1             0             0
Subject No Longer Met Study Criteria             4             0             0
Other             2             1             1
[1]
Completed=Continuing in Treatment Period
Period Title: Follow-Up Period
Started 92 [1] 11 [1] 19 [1]
Completed 92 [2] 11 [2] 19 [2]
Not Completed 0 0 0
[1]
Participants could enter follow-up after discontinuing treatment for safety assessments
[2]
Completed=Continuing in Follow-up Period; Study on-going
Arm/Group Title Nivolumab 3 mg/kg (IV) Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel) Total
Hide Arm/Group Description Nivolumab 3 mg/kg solution for injection by intravenous (IV), every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Dacarbazine: 1000mg/m2, Powder for IV solution, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Carboplatin: Area under the concentration-time curve (AUC) 6, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Paclitaxel: 175 mg/ m2, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Total of all reporting groups
Overall Number of Baseline Participants 272 133 405
Hide Baseline Analysis Population Description
All Randomized Participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 272 participants 133 participants 405 participants
58.7  (14.12) 60.3  (12.43) 59.2  (13.59)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 272 participants 133 participants 405 participants
< 65 years
177
  65.1%
80
  60.2%
257
  63.5%
>=65 years and < 75 years
55
  20.2%
37
  27.8%
92
  22.7%
>=75 years and < 85 years
36
  13.2%
15
  11.3%
51
  12.6%
>=85 years
4
   1.5%
1
   0.8%
5
   1.2%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 272 participants 133 participants 405 participants
Female
96
  35.3%
48
  36.1%
144
  35.6%
Male
176
  64.7%
85
  63.9%
261
  64.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 272 participants 133 participants 405 participants
White
269
  98.9%
129
  97.0%
398
  98.3%
Black or African American
1
   0.4%
2
   1.5%
3
   0.7%
Asian
2
   0.7%
0
   0.0%
2
   0.5%
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Other
0
   0.0%
2
   1.5%
2
   0.5%
Quantifiable Programmed Death-ligand 1 (PD-L1) Expression  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 272 participants 133 participants 405 participants
248
  91.2%
99
  74.4%
347
  85.7%
1.Primary Outcome
Title Objective Response Rate (ORR)
Hide Description ORR=number of participants with a Best Overall Response (BOR) of complete response (CR) or partial response (PR) divided by the number of randomized participants and reported as a percentage. BOR was defined as the best response designation, as determined by the independent review committee (IRC), recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of subsequent therapy (including tumor-directed radiotherapy and tumor-directed surgery), whichever occurred first. For participants without documented progression or subsequent therapy, all available response designations contributed to the BOR assessment. 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. Analysis made at Primary Endpoint; Study On-going
Time Frame From date of randomization to the date of objectively documented progression, date of death, or the date of subsequent therapy; approx. 16 months
Hide Outcome Measure Data
Hide Analysis Population Description
All Randomized Participants: All participants randomized to any treatment group
Arm/Group Title Nivolumab 3 mg/kg (IV) Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution for injection by intravenous (IV), every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Dacarbazine: 1000mg/m2, Powder for IV solution, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Carboplatin: Area under the concentration-time curve (AUC) 6, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Paclitaxel: 175 mg/ m2, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Overall Number of Participants Analyzed 272 133
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
27.2
(22.0 to 32.9)
9.8
(5.3 to 16.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab 3 mg/kg (IV), Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
Comments Unweighted ORR difference with 95% CI.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Objective Response Rate
Estimated Value 17.4
Confidence Interval (2-Sided) 95%
9.5 to 24.3
Estimation Comments Nivolumab vs Investigator's Choice.
2.Primary Outcome
Title Median Overall Survival (OS) at Primary Endpoint
Hide Description Overall Survival (OS) was defined the time between the date of randomization to the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive. OS was followed continuously while participants were on the study drug and every 3 months via in-person or phone contact after participants discontinued the study drug. This interim OS analysis was performed on all randomized subjects when at least 169 events had been observed. Analysis made at Primary Endpoint; Study On-going.
Time Frame From the date of randomization to the date of death; up to 37 months
Hide Outcome Measure Data
Hide Analysis Population Description
All Randomized Participants: All participants randomized to any treatment group
Arm/Group Title Nivolumab 3 mg/kg (IV) Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution for injection by intravenous (IV), every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Dacarbazine: 1000mg/m2, Powder for IV solution, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Carboplatin: Area under the concentration-time curve (AUC) 6, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Paclitaxel: 175 mg/ m2, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Overall Number of Participants Analyzed 272 133
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: months
15.74
(12.88 to 19.88)
14.39
(11.66 to 18.17)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab 3 mg/kg (IV), Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
Comments Nivolumab 3 mg/kg (IV) vs Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7164
Comments [Not Specified]
Method Log Rank
Comments Log-rank Test stratified by BRAF status, prior anti-CTLA-4 benefit, and PD-L1 status (Interactive Voice Response System (IVRS) source).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95.54%
0.73 to 1.24
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Median Months of Progression-free Survival (PFS) Per Independent Radiology Review Committee (IRC/IRRC)
Hide Description PFS=time from randomization to the date of the first documented progression or death due to any cause, whichever first. Participants who (1) died without a reported progression were considered to have progressed on the date of their death, (2) did not progress or die were censored on the date of their last evaluable tumor assessment, (3) did not have any on study tumor assessments and did not die were censored on the date they were randomized, and (4) started any subsequent anti-cancer therapy (including tumor-directed radiotherapy or surgery) without a prior reported progression were censored at the last evaluable tumor assessment prior to or upon initiation of the subsequent anti-cancer therapy. Per RECIST 1.1, progression is >= 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes baseline sum if smallest on study). The sum must demonstrate an absolute increase of >= 5 mm. Analysis made at Primary Endpoint; Study On-going
Time Frame From the date of randomization to the date of the first documented progression or death; up to 37 months
Hide Outcome Measure Data
Hide Analysis Population Description
All Randomized Participants: All participants randomized to any treatment group
Arm/Group Title Nivolumab 3 mg/kg (IV) Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution for injection by intravenous (IV), every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Dacarbazine: 1000mg/m2, Powder for IV solution, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Carboplatin: Area under the concentration-time curve (AUC) 6, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Paclitaxel: 175 mg/ m2, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Overall Number of Participants Analyzed 272 133
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: months
3.12
(2.33 to 3.52)
3.65
(2.30 to 5.29)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab 3 mg/kg (IV), Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
Comments Stratified Cox proportional hazard model.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95.1%
0.78 to 1.36
Estimation Comments Hazard Ratio is Nivolumab 3 mg/kg (IV) over Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
4.Secondary Outcome
Title Objective Response Rate (ORR) by Baseline PD-L1 Expression
Hide Description PD-L1 expression evaluated as a predictive biomarker for ORR by analyzing the interaction between PD-L1 expression and treatment arms. Randomized participants with an Indeterminate PD-L1 result per the verified assay were categorized as "Subjects without Tumor Tissue Samples". ORR=number of participants with a Best Overall Response (BOR) of complete response (CR) or partial response (PR) divided by number of randomized participants and reported as a percentage. Analysis made at Primary Endpoint; Study On-going.
Time Frame From date of randomization to the date of objectively documented progression or the date of subsequent therapy; approx. 16 months
Hide Outcome Measure Data
Hide Analysis Population Description
All PD-L1 Evaluable Participants; Randomized participants among the ORR population who had a tumor biopsy specimen assessed for PD-L1 expression with the validated assay and for which quantifiable tumor PD-L1 levels were discernible.
Arm/Group Title Nivolumab 3 mg/kg (IV) Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution for injection by intravenous (IV), every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Dacarbazine: 1000mg/m2, Powder for IV solution, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Carboplatin: Area under the concentration-time curve (AUC) 6, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Paclitaxel: 175 mg/ m2, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Overall Number of Participants Analyzed 267 131
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
<5% PD-L1 expression (n=137, 58
15.3
(9.7 to 22.5)
13.8
(6.1 to 25.4)
>=5% PD-L1 expression (n=111, 41)
43.2
(33.9 to 53.0)
12.2
(4.1 to 26.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab 3 mg/kg (IV), Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
Comments For <5% PD-L1 expression. Ratio of Nivolumab over Investigator's Choice
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.44 to 3.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Nivolumab 3 mg/kg (IV), Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
Comments For >=5% PD-L1 expression. Ratio of Nivolumab over Investigator's Choice
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.49
Confidence Interval (2-Sided) 95%
1.92 to 19.08
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Median Overall Survival (OS) Time in Months by Baseline PD-L1 Expression
Hide Description PD-L1 expression evaluated as a predictive biomarker for OS by analyzing the interaction between PD-L1 expression and treatment arms. Randomized participants with an Indeterminate PD-L1 result per the verified assay were categorized as "Subjects without Tumor Tissue Samples". Overall Survival (OS) was defined the time between the date of randomization to the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive. OS was followed continuously while participants were on the study drug and every 3 months via in-person or phone contact after participants discontinued the study drug. The interim OS analysis was performed on all randomized subjects when at least 169 events had been observed. Analysis made at Primary Endpoint; Study On-going.
Time Frame From the date of randomization to the date of death; up to 37 months
Hide Outcome Measure Data
Hide Analysis Population Description
All PD-L1 Evaluable Participants; Randomized participants among the OS population who had a tumor biopsy specimen assessed for PD-L1 expression with the validated assay and for which quantifiable tumor PD-L1 levels were discernible.
Arm/Group Title Nivolumab 3 mg/kg (IV) Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution for injection by intravenous (IV), every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Dacarbazine: 1000mg/m2, Powder for IV solution, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Carboplatin: Area under the concentration-time curve (AUC) 6, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Paclitaxel: 175 mg/ m2, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Overall Number of Participants Analyzed 267 131
Median (95% Confidence Interval)
Unit of Measure: months
<5% PD-L1 expression (n=137, 58
10.61
(7.85 to 13.21)
11.27
(8.02 to 17.91)
>=5% PD-L1 expression (n=111, 41)
NA [1] 
(21.98 to NA)
15.44
(11.50 to 19.75)
[1]
Upper Limit Not Yet Reached
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab 3 mg/kg (IV), Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
Comments For <5% PD-L1 expression. Ratio of Nivolumab over Investigator's Choice
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio, log
Estimated Value 1.22
Confidence Interval (2-Sided) 95%
0.85 to 1.74
Estimation Comments From unstratified Cox proportional hazard model using randomized arm as single covariate.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Nivolumab 3 mg/kg (IV), Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
Comments For >=5% PD-L1 expression. Ratio of Nivolumab over Investigator's Choice
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.55
Confidence Interval (2-Sided) 95%
0.35 to 0.87
Estimation Comments from unstratified Cox proportional hazard model using randomized arm as single covariate.
6.Secondary Outcome
Title Mean Change From Baseline in Health-related Quality of Life (HRQoL) Global Health Status Scores
Hide Description Health-related Quality of Life (HRQoL) was assessed with the EORTC QLQ-C30 questionnaire, which is the most commonly used quality-of-life instrument in oncology trials. The instrument's 30 items were divided among 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a global health/quality of life scale. Raw scores for the EORTC QLQ-C30 were transformed to a 0-100 metric. Higher scores for all functional scales and Global Health Status=better HRQoL; an increase from baseline indicates improvement in HRQoL. Lower scores for symptom scales=better HRQoL; a decline from baseline for symptom scales =improvement in symptoms compared to baseline. A 10 point difference on a 100 point scale between treatments was considered clinically significant.
Time Frame From Baseline (Day1) to second Follow-Up; up to 37 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with a baseline measurement and at least one on-study assessment; n=number of participants evaluable
Arm/Group Title Nivolumab 3 mg/kg (IV) Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
Hide Arm/Group Description:
Nivolumab 3 mg/kg solution for injection by intravenous (IV), every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Dacarbazine: 1000mg/m2, Powder for IV solution, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Carboplatin: Area under the concentration-time curve (AUC) 6, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Paclitaxel: 175 mg/ m2, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Overall Number of Participants Analyzed 272 133
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 12 (n=110, 29) 1.4  (17.9) -5.7  (17.4)
Week 24 (n=74, 9) 3.7  (18.9) -8.3  (17.2)
Week 30 (n=56, 4) 1.0  (17.3) -6.3  (8.0)
Week 36 (n=53, 2) 2.7  (14.0) 4.2  (5.9)
Week 42 (n=45, 3) 0.2  (15.8) -5.6  (12.7)
Week 48 (n=42, 1) -0.6  (19.4) 16.7 [1]   (NA)
Week 54 (n=35, 1) -0.5  (16.5) 16.7 [1]   (NA)
Week 60 (n=36, 1) -0.2  (14.0) 8.3 [1]   (NA)
Week 66 (n=34, 1) 1.5  (14.3) 0.0 [1]   (NA)
Week 72 (n=30, 0) 0.3  (13.9) NA [2]   (NA)
Week 78 (n=28, 0) 2.7  (16.7) NA [2]   (NA)
Week 84 (n=27, 0) 3.1  (14.5) NA [2]   (NA)
Week 90 (n=25, 0) 4.0  (13.8) NA [2]   (NA)
Week 96 (n=23, 0) 2.2  (19.2) NA [2]   (NA)
Week 102 (n=21, 0) 6.0  (14.2) NA [2]   (NA)
Week 108 (n=15, 0) 2.2  (19.0) NA [2]   (NA)
Week 114 (n=15, 0) 1.1  (12.1) NA [2]   (NA)
Week 120 (n=10, 0) 2.5  (15.7) NA [2]   (NA)
Week 126 (n=8, 0) 8.3  (11.8) NA [2]   (NA)
Week 132 (n=2, 0) 11.7  (12.6) NA [2]   (NA)
Week 138 (n=5, 0) 0.0  (0.0) NA [2]   (NA)
Week 144 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Week 150 (n=1, 0) -16.7 [1]   (NA) NA [2]   (NA)
Follow-up 1 (n=72, 21) -9.8  (22.3) -10.7  (17.7)
Follow-up 2 (n=54, 28) -3.4  (18.4) -3.3  (12.1)
[1]
Sample size is too small to calculate standard deviation
[2]
No participants in this arm were available
Time Frame Date of first dose to date of last dose of study therapy plus 30 days; assessed up to 37 months
Adverse Event Reporting Description

All Treated Participants

Study Initiated: December 21, 2012 PE Study Completion: February 16, 2016 Study On-going

 
Arm/Group Title Nivolumab 3 mg/kg (IV) Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
Hide Arm/Group Description Nivolumab 3 mg/kg solution for injection by intravenous (IV), every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Dacarbazine: 1000mg/m2, Powder for IV solution, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Carboplatin: Area under the concentration-time curve (AUC) 6, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Paclitaxel: 175 mg/ m2, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

All-Cause Mortality
Nivolumab 3 mg/kg (IV) Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
Affected / at Risk (%) Affected / at Risk (%)
Total   172/268 (64.18%)   72/102 (70.59%) 
Hide Serious Adverse Events
Nivolumab 3 mg/kg (IV) Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
Affected / at Risk (%) Affected / at Risk (%)
Total   156/268 (58.21%)   24/102 (23.53%) 
Blood and lymphatic system disorders     
Febrile neutropenia  1  0/268 (0.00%)  2/102 (1.96%) 
Haemorrhagic anaemia  1  1/268 (0.37%)  0/102 (0.00%) 
Splenic lesion  1  1/268 (0.37%)  0/102 (0.00%) 
Anaemia  1  1/268 (0.37%)  2/102 (1.96%) 
Lymphadenopathy  1  1/268 (0.37%)  0/102 (0.00%) 
Thrombocytopenia  1  0/268 (0.00%)  1/102 (0.98%) 
Splenic haematoma  1  1/268 (0.37%)  0/102 (0.00%) 
Cardiac disorders     
Cardiac failure  1  1/268 (0.37%)  0/102 (0.00%) 
Pericarditis  1  1/268 (0.37%)  0/102 (0.00%) 
Sinus tachycardia  1  1/268 (0.37%)  0/102 (0.00%) 
Cardio-respiratory arrest  1  1/268 (0.37%)  0/102 (0.00%) 
Atrial flutter  1  2/268 (0.75%)  0/102 (0.00%) 
Myocardial infarction  1  1/268 (0.37%)  0/102 (0.00%) 
Ventricular arrhythmia  1  1/268 (0.37%)  0/102 (0.00%) 
Acute myocardial infarction  1  1/268 (0.37%)  0/102 (0.00%) 
Atrial fibrillation  1  4/268 (1.49%)  0/102 (0.00%) 
Cardiac arrest  1  3/268 (1.12%)  0/102 (0.00%) 
Endocrine disorders     
Adrenal haemorrhage  1  1/268 (0.37%)  0/102 (0.00%) 
Adrenal insufficiency  1  2/268 (0.75%)  0/102 (0.00%) 
Hypothyroidism  1  1/268 (0.37%)  0/102 (0.00%) 
Eye disorders     
Retinal detachment  1  1/268 (0.37%)  0/102 (0.00%) 
Gastrointestinal disorders     
Diarrhoea  1  2/268 (0.75%)  2/102 (1.96%) 
Pancreatitis  1  2/268 (0.75%)  0/102 (0.00%) 
Colitis  1  1/268 (0.37%)  0/102 (0.00%) 
Constipation  1  1/268 (0.37%)  0/102 (0.00%) 
Diverticular perforation  1  1/268 (0.37%)  0/102 (0.00%) 
Inguinal hernia  1  1/268 (0.37%)  0/102 (0.00%) 
Upper gastrointestinal haemorrhage  1  1/268 (0.37%)  0/102 (0.00%) 
Ascites  1  1/268 (0.37%)  0/102 (0.00%) 
Lower gastrointestinal haemorrhage  1  1/268 (0.37%)  0/102 (0.00%) 
Nausea  1  2/268 (0.75%)  1/102 (0.98%) 
Vomiting  1  2/268 (0.75%)  3/102 (2.94%) 
Small intestinal obstruction  1  3/268 (1.12%)  0/102 (0.00%) 
Abdominal pain  1  5/268 (1.87%)  0/102 (0.00%) 
Abdominal pain upper  1  1/268 (0.37%)  0/102 (0.00%) 
Dysphagia  1  1/268 (0.37%)  0/102 (0.00%) 
Haematemesis  1  1/268 (0.37%)  0/102 (0.00%) 
General disorders     
Chest pain  1  1/268 (0.37%)  0/102 (0.00%) 
Fatigue  1  2/268 (0.75%)  2/102 (1.96%) 
Pelvic mass  1  1/268 (0.37%)  0/102 (0.00%) 
General physical health deterioration  1  4/268 (1.49%)  0/102 (0.00%) 
Pyrexia  1  4/268 (1.49%)  2/102 (1.96%) 
Infusion site extravasation  1  1/268 (0.37%)  0/102 (0.00%) 
Thrombosis in device  1  1/268 (0.37%)  0/102 (0.00%) 
Asthenia  1  1/268 (0.37%)  0/102 (0.00%) 
Gait disturbance  1  1/268 (0.37%)  0/102 (0.00%) 
Ulcer  1  1/268 (0.37%)  0/102 (0.00%) 
Pain  1  1/268 (0.37%)  1/102 (0.98%) 
Hepatobiliary disorders     
Hepatic haemorrhage  1  1/268 (0.37%)  0/102 (0.00%) 
Hepatocellular injury  1  1/268 (0.37%)  0/102 (0.00%) 
Immune system disorders     
Hypersensitivity  1  1/268 (0.37%)  0/102 (0.00%) 
Infections and infestations     
Pneumonia  1  7/268 (2.61%)  0/102 (0.00%) 
Wound infection  1  1/268 (0.37%)  0/102 (0.00%) 
Clostridium difficile colitis  1  1/268 (0.37%)  0/102 (0.00%) 
Gastroenteritis  1  1/268 (0.37%)  0/102 (0.00%) 
Cystitis  1  1/268 (0.37%)  0/102 (0.00%) 
Erysipelas  1  2/268 (0.75%)  1/102 (0.98%) 
Influenza  1  1/268 (0.37%)  0/102 (0.00%) 
Lower respiratory tract infection  1  1/268 (0.37%)  0/102 (0.00%) 
Pneumonia pseudomonal  1  1/268 (0.37%)  0/102 (0.00%) 
Cellulitis  1  2/268 (0.75%)  0/102 (0.00%) 
Infection  1  2/268 (0.75%)  0/102 (0.00%) 
Neutropenic sepsis  1  0/268 (0.00%)  1/102 (0.98%) 
Bronchitis  1  1/268 (0.37%)  0/102 (0.00%) 
Sepsis  1  3/268 (1.12%)  0/102 (0.00%) 
Device related infection  1  2/268 (0.75%)  0/102 (0.00%) 
Diverticulitis  1  1/268 (0.37%)  0/102 (0.00%) 
Herpes zoster  1  1/268 (0.37%)  0/102 (0.00%) 
Clostridium difficile infection  1  1/268 (0.37%)  0/102 (0.00%) 
Febrile infection  1  0/268 (0.00%)  1/102 (0.98%) 
Urinary tract infection  1  3/268 (1.12%)  0/102 (0.00%) 
Urosepsis  1  1/268 (0.37%)  0/102 (0.00%) 
Injury, poisoning and procedural complications     
Radiation necrosis  1  1/268 (0.37%)  0/102 (0.00%) 
Ankle fracture  1  1/268 (0.37%)  0/102 (0.00%) 
Subdural haematoma  1  1/268 (0.37%)  0/102 (0.00%) 
Infusion related reaction  1  1/268 (0.37%)  0/102 (0.00%) 
Spinal fracture  1  1/268 (0.37%)  0/102 (0.00%) 
Femur fracture  1  1/268 (0.37%)  0/102 (0.00%) 
Rib fracture  1  1/268 (0.37%)  0/102 (0.00%) 
Toxicity to various agents  1  1/268 (0.37%)  1/102 (0.98%) 
Wound dehiscence  1  1/268 (0.37%)  0/102 (0.00%) 
Postoperative ileus  1  1/268 (0.37%)  0/102 (0.00%) 
Investigations     
Liver function test abnormal  1  3/268 (1.12%)  0/102 (0.00%) 
Alanine aminotransferase increased  1  2/268 (0.75%)  0/102 (0.00%) 
Aspartate aminotransferase increased  1  1/268 (0.37%)  0/102 (0.00%) 
Blood alkaline phosphatase increased  1  1/268 (0.37%)  0/102 (0.00%) 
Ejection fraction  1  1/268 (0.37%)  0/102 (0.00%) 
Hepatic enzyme increased  1  1/268 (0.37%)  0/102 (0.00%) 
Metabolism and nutrition disorders     
Hypertriglyceridaemia  1  1/268 (0.37%)  0/102 (0.00%) 
Dehydration  1  5/268 (1.87%)  0/102 (0.00%) 
Hypoglycaemia  1  1/268 (0.37%)  1/102 (0.98%) 
Hyponatraemia  1  1/268 (0.37%)  0/102 (0.00%) 
Hyperglycaemia  1  2/268 (0.75%)  0/102 (0.00%) 
Failure to thrive  1  1/268 (0.37%)  0/102 (0.00%) 
Hypercalcaemia  1  1/268 (0.37%)  0/102 (0.00%) 
Hypokalaemia  1  1/268 (0.37%)  0/102 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/268 (0.37%)  1/102 (0.98%) 
Back pain  1  6/268 (2.24%)  2/102 (1.96%) 
Arthritis  1  1/268 (0.37%)  0/102 (0.00%) 
Flank pain  1  0/268 (0.00%)  1/102 (0.98%) 
Osteoarthritis  1  4/268 (1.49%)  0/102 (0.00%) 
Pathological fracture  1  2/268 (0.75%)  0/102 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Melanoma recurrent  1  1/268 (0.37%)  0/102 (0.00%) 
Neoplasm malignant  1  1/268 (0.37%)  0/102 (0.00%) 
Prostate cancer  1  2/268 (0.75%)  0/102 (0.00%) 
Tumour associated fever  1  0/268 (0.00%)  1/102 (0.98%) 
Cancer pain  1  1/268 (0.37%)  0/102 (0.00%) 
Metastases to pleura  1  1/268 (0.37%)  0/102 (0.00%) 
Metastatic pain  1  2/268 (0.75%)  0/102 (0.00%) 
Parathyroid tumour benign  1  1/268 (0.37%)  0/102 (0.00%) 
Tumour fistulisation  1  2/268 (0.75%)  0/102 (0.00%) 
Malignant melanoma  1  3/268 (1.12%)  1/102 (0.98%) 
Keratoacanthoma  1  1/268 (0.37%)  0/102 (0.00%) 
Tumour pain  1  2/268 (0.75%)  0/102 (0.00%) 
Basal cell carcinoma  1  1/268 (0.37%)  0/102 (0.00%) 
Metastases to adrenals  1  1/268 (0.37%)  0/102 (0.00%) 
Metastases to central nervous system  1  1/268 (0.37%)  0/102 (0.00%) 
Metastatic malignant melanoma  1  5/268 (1.87%)  0/102 (0.00%) 
Skin neoplasm bleeding  1  0/268 (0.00%)  1/102 (0.98%) 
Malignant neoplasm progression  1  38/268 (14.18%)  5/102 (4.90%) 
Squamous cell carcinoma  1  4/268 (1.49%)  0/102 (0.00%) 
Nervous system disorders     
Status epilepticus  1  1/268 (0.37%)  0/102 (0.00%) 
Dizziness  1  1/268 (0.37%)  0/102 (0.00%) 
Seizure  1  2/268 (0.75%)  0/102 (0.00%) 
Demyelination  1  1/268 (0.37%)  0/102 (0.00%) 
Haemorrhage intracranial  1  1/268 (0.37%)  0/102 (0.00%) 
Transient ischaemic attack  1  0/268 (0.00%)  1/102 (0.98%) 
Brain oedema  1  1/268 (0.37%)  0/102 (0.00%) 
Headache  1  1/268 (0.37%)  0/102 (0.00%) 
Aphasia  1  1/268 (0.37%)  0/102 (0.00%) 
Autoimmune neuropathy  1  1/268 (0.37%)  0/102 (0.00%) 
Cerebrovascular accident  1  2/268 (0.75%)  0/102 (0.00%) 
Psychiatric disorders     
Burnout syndrome  1  1/268 (0.37%)  0/102 (0.00%) 
Confusional state  1  3/268 (1.12%)  0/102 (0.00%) 
Renal and urinary disorders     
Nephrolithiasis  1  1/268 (0.37%)  0/102 (0.00%) 
Tubulointerstitial nephritis  1  1/268 (0.37%)  0/102 (0.00%) 
Acute kidney injury  1  0/268 (0.00%)  2/102 (1.96%) 
Hydronephrosis  1  2/268 (0.75%)  0/102 (0.00%) 
Renal impairment  1  1/268 (0.37%)  0/102 (0.00%) 
Renal failure  1  2/268 (0.75%)  0/102 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  1/268 (0.37%)  0/102 (0.00%) 
Dyspnoea  1  5/268 (1.87%)  3/102 (2.94%) 
Hypoxia  1  2/268 (0.75%)  0/102 (0.00%) 
Haemoptysis  1  2/268 (0.75%)  0/102 (0.00%) 
Pleural effusion  1  2/268 (0.75%)  1/102 (0.98%) 
Pneumonitis  1  1/268 (0.37%)  0/102 (0.00%) 
Pulmonary embolism  1  2/268 (0.75%)  0/102 (0.00%) 
Interstitial lung disease  1  1/268 (0.37%)  0/102 (0.00%) 
Skin and subcutaneous tissue disorders     
Skin haemorrhage  1  0/268 (0.00%)  1/102 (0.98%) 
Vascular disorders     
Superior vena cava syndrome  1  1/268 (0.37%)  0/102 (0.00%) 
Hypertension  1  1/268 (0.37%)  0/102 (0.00%) 
Hypotension  1  3/268 (1.12%)  1/102 (0.98%) 
Deep vein thrombosis  1  1/268 (0.37%)  0/102 (0.00%) 
Embolism  1  1/268 (0.37%)  0/102 (0.00%) 
Embolism arterial  1  0/268 (0.00%)  1/102 (0.98%) 
1
Term from vocabulary, MedDRA 18.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Nivolumab 3 mg/kg (IV) Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
Affected / at Risk (%) Affected / at Risk (%)
Total   254/268 (94.78%)   95/102 (93.14%) 
Blood and lymphatic system disorders     
Anaemia  1  60/268 (22.39%)  30/102 (29.41%) 
Leukopenia  1  4/268 (1.49%)  9/102 (8.82%) 
Thrombocytopenia  1  8/268 (2.99%)  11/102 (10.78%) 
Neutropenia  1  2/268 (0.75%)  23/102 (22.55%) 
Endocrine disorders     
Hypothyroidism  1  25/268 (9.33%)  0/102 (0.00%) 
Gastrointestinal disorders     
Diarrhoea  1  82/268 (30.60%)  18/102 (17.65%) 
Constipation  1  48/268 (17.91%)  22/102 (21.57%) 
Dyspepsia  1  21/268 (7.84%)  3/102 (2.94%) 
Nausea  1  85/268 (31.72%)  42/102 (41.18%) 
Vomiting  1  54/268 (20.15%)  24/102 (23.53%) 
Dry mouth  1  14/268 (5.22%)  2/102 (1.96%) 
Abdominal pain  1  45/268 (16.79%)  9/102 (8.82%) 
Abdominal pain upper  1  21/268 (7.84%)  7/102 (6.86%) 
General disorders     
Oedema peripheral  1  38/268 (14.18%)  5/102 (4.90%) 
Fatigue  1  128/268 (47.76%)  50/102 (49.02%) 
Pyrexia  1  48/268 (17.91%)  9/102 (8.82%) 
Chills  1  18/268 (6.72%)  3/102 (2.94%) 
Asthenia  1  32/268 (11.94%)  9/102 (8.82%) 
Influenza like illness  1  16/268 (5.97%)  4/102 (3.92%) 
Pain  1  26/268 (9.70%)  3/102 (2.94%) 
Infections and infestations     
Nasopharyngitis  1  27/268 (10.07%)  4/102 (3.92%) 
Upper respiratory tract infection  1  20/268 (7.46%)  2/102 (1.96%) 
Urinary tract infection  1  20/268 (7.46%)  4/102 (3.92%) 
Injury, poisoning and procedural complications     
Infusion related reaction  1  3/268 (1.12%)  9/102 (8.82%) 
Investigations     
Alanine aminotransferase increased  1  24/268 (8.96%)  3/102 (2.94%) 
Aspartate aminotransferase increased  1  34/268 (12.69%)  5/102 (4.90%) 
White blood cell count decreased  1  6/268 (2.24%)  9/102 (8.82%) 
Blood creatinine increased  1  19/268 (7.09%)  1/102 (0.98%) 
Weight decreased  1  23/268 (8.58%)  6/102 (5.88%) 
Neutrophil count decreased  1  0/268 (0.00%)  8/102 (7.84%) 
Platelet count decreased  1  8/268 (2.99%)  9/102 (8.82%) 
Blood alkaline phosphatase increased  1  21/268 (7.84%)  3/102 (2.94%) 
Metabolism and nutrition disorders     
Hyponatraemia  1  23/268 (8.58%)  1/102 (0.98%) 
Hypoalbuminaemia  1  18/268 (6.72%)  0/102 (0.00%) 
Decreased appetite  1  50/268 (18.66%)  20/102 (19.61%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  61/268 (22.76%)  17/102 (16.67%) 
Back pain  1  52/268 (19.40%)  0/102 (0.00%) 
Muscle spasms  1  14/268 (5.22%)  1/102 (0.98%) 
Myalgia  1  26/268 (9.70%)  10/102 (9.80%) 
Pain in extremity  1  34/268 (12.69%)  11/102 (10.78%) 
Musculoskeletal pain  1  32/268 (11.94%)  4/102 (3.92%) 
Nervous system disorders     
Neuropathy peripheral  1  11/268 (4.10%)  10/102 (9.80%) 
Dizziness  1  25/268 (9.33%)  5/102 (4.90%) 
Dysgeusia  1  16/268 (5.97%)  3/102 (2.94%) 
Headache  1  40/268 (14.93%)  11/102 (10.78%) 
Paraesthesia  1  12/268 (4.48%)  12/102 (11.76%) 
Psychiatric disorders     
Insomnia  1  32/268 (11.94%)  6/102 (5.88%) 
Anxiety  1  17/268 (6.34%)  1/102 (0.98%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  66/268 (24.63%)  7/102 (6.86%) 
Dyspnoea  1  48/268 (17.91%)  14/102 (13.73%) 
Skin and subcutaneous tissue disorders     
Rash  1  51/268 (19.03%)  5/102 (4.90%) 
Alopecia  1  8/268 (2.99%)  29/102 (28.43%) 
Rash maculo-papular  1  20/268 (7.46%)  2/102 (1.96%) 
Vitiligo  1  31/268 (11.57%)  0/102 (0.00%) 
Dry skin  1  20/268 (7.46%)  1/102 (0.98%) 
Pruritus  1  70/268 (26.12%)  3/102 (2.94%) 
Vascular disorders     
Hypertension  1  22/268 (8.21%)  3/102 (2.94%) 
1
Term from vocabulary, MedDRA 18.1
Indicates events were collected by systematic assessment
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
Layout table for Results Point of Contact information
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
EMail: Clinical.Trials@bms.com
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01721746    
Other Study ID Numbers: CA209-037
2012-001828-35 ( EudraCT Number )
First Submitted: November 2, 2012
First Posted: November 6, 2012
Results First Submitted: February 1, 2017
Results First Posted: March 22, 2017
Last Update Posted: May 18, 2020