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Trial record 96 of 506 for:    melanoma phase III

Study of Nivolumab (BMS-936558) Compared With Dacarbazine in Untreated, Unresectable, or Metastatic Melanoma (CheckMate 066)

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: NCT01721772
Recruitment Status : Active, not recruiting
First Posted : November 6, 2012
Results First Posted : February 25, 2016
Last Update Posted : August 8, 2018
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Melanoma
Interventions Biological: BMS-936558 (Nivolumab)
Biological: Placebo matching BMS-936558 (Nivolumab)
Drug: Dacarbazine
Drug: Placebo matching Dacarbazine
Enrollment 583
Recruitment Details  
Pre-assignment Details Of 583 participants enrolled, 418 were randomized (210 to nivolumab, 208 to dacarbazine) and 411 received treatment (206 with nivolumab, 205 with dacarbazine).
Arm/Group Title Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab
Hide Arm/Group Description Participants received nivolumab, 3 mg/kg, solution administered Intravenously (IV) every 2 weeks with placebo-matching dacarbazine solution administered IV every 3 weeks, until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion Participants received dacarbazine 1000 mg/m^2, solution administered IV every 3 weeks with placebo-matching nivolumab solution administered IV every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
Period Title: Overall Study
Started 206 205
Completed 95 [1] 13 [1]
Not Completed 111 192
Reason Not Completed
Disease progression             96             175
Study drug toxicity             5             7
Unrelated adverse event             2             3
Withdrawal by Subject             7             5
Maximum clinical benefit             1             1
Not specified             0             1
[1]
Continuing in treatment period
Arm/Group Title Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab Total
Hide Arm/Group Description Participants received nivolumab, 3 mg/kg, solution administered Intravenously (IV) every 2 weeks with placebo-matching dacarbazine solution administered IV every 3 weeks, until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion Participants received dacarbazine 1000 mg/m^2, solution administered IV every 3 weeks with placebo-matching nivolumab solution administered IV every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion Total of all reporting groups
Overall Number of Baseline Participants 210 208 418
Hide Baseline Analysis Population Description
All participants randomized to receive treatment
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 210 participants 208 participants 418 participants
61.6  (13.00) 63.7  (12.60) 62.7  (12.83)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 210 participants 208 participants 418 participants
Younger than 65 years 106 94 200
65 to younger than 75 years 77 74 151
75 years and older 27 40 67
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 210 participants 208 participants 418 participants
Female
89
  42.4%
83
  39.9%
172
  41.1%
Male
121
  57.6%
125
  60.1%
246
  58.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 210 participants 208 participants 418 participants
White 209 207 416
Black or African American 0 0 0
Asian 0 1 1
American Indian or Alaskan native 0 0 0
Other 1 0 1
M-stage at study entry   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 210 participants 208 participants 418 participants
M0 17 13 30
M1a 21 20 41
M1b 44 48 92
M1c 128 127 255
[1]
Measure Description: M-stage=melanoma stage by American Joint Committee on Cancer Melanoma Staging and Classification, 2009. M0=no distant metastases; M1a=distant skin, subcutaneous, or nodal metastases; M1b=lung metastases; M1c=all other visceral metastases
Stratification programmed cell death ligand 1 status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 210 participants 208 participants 418 participants
Positive 74 74 148
Negative/indeterminate 136 134 270
Time from initial diagnosis  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 210 participants 208 participants 418 participants
1.93
(0.1 to 32.6)
1.65
(0.1 to 22.2)
1.83
(0.1 to 32.6)
Participants with at least 1 lesion  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 210 participants 208 participants 418 participants
209 208 417
Site of lesion  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 210 participants 208 participants 418 participants
Bone 25 18 43
Intestine 6 3 9
Liver 68 60 128
Lung 128 125 253
Lymph node 120 121 241
Other 54 47 101
Skin 23 37 60
Soft tissue 40 58 98
Visceral, other 30 50 80
1.Primary Outcome
Title Overall Survival (OS)
Hide Description OS is defined as the time between the date of randomization and the date of death. For those without documentation of death, OS will be censored on the last date the participant was known to be alive.
Time Frame From date of randomization to date of death. For those without documentation of death, to the last date the participant was known to be alive, assessed to 17 months.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized to receive treatment
Arm/Group Title Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab
Hide Arm/Group Description:
Participants received nivolumab, 3 mg/kg, solution administered Intravenously (IV) every 2 weeks with placebo-matching dacarbazine solution administered IV every 3 weeks, until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
Participants received dacarbazine 1000 mg/m^2, solution administered IV every 3 weeks with placebo-matching nivolumab solution administered IV every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
Overall Number of Participants Analyzed 210 208
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
10.84
(9.33 to 12.09)
[1]
Median survival was not estimable due to small number of deaths in this arm. Of 210 randomized patients, 50 have died at the time of analysis. Lower confidence limits for the survivor function are <0.50 and as a result, cannot be estimated
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine, Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Stratified Log Rank Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
0.30 to 0.60
Estimation Comments [Not Specified]
2.Primary Outcome
Title Overall Survival (OS) Rate
Hide Description OS rate is calculated as the percentage of participants who have not died divided by the total number of participants in the arm, based on Kaplan-Meier estimates
Time Frame Randomization to 6 months and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized to receive treatment
Arm/Group Title Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab
Hide Arm/Group Description:
Participants received nivolumab, 3 mg/kg, solution administered Intravenously (IV) every 2 weeks with placebo-matching dacarbazine solution administered IV every 3 weeks, until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
Participants received dacarbazine 1000 mg/m^2, solution administered IV every 3 weeks with placebo-matching nivolumab solution administered IV every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
Overall Number of Participants Analyzed 210 208
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
At 6 months
84.1
(78.3 to 88.5)
71.8
(64.9 to 77.6)
At 12 months
72.9
(65.5 to 78.9)
42.1
(33.0 to 50.9)
3.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description Investigator-assessed PFS is defined as the time from randomization to the date of the first documented progression, as determined by the investigator, or death due to any cause, whichever occurs first. Patients who died without progressing were considered to have progressed on the date of their death. Those who did not progress or die were censored on the date of their last evaluable tumor assessment. Patients who did not have any on-study tumor assessments and did not die were censored on their date of randomization. Those who started any subsequent anticancer therapy without a prior reported progression were censored on the date of their last evaluable tumor assessment prior to initiation of subsequent anticancer therapy.
Time Frame From date of randomization to date of disease progression or death, assessed to 17 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized to receive treatment
Arm/Group Title Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab
Hide Arm/Group Description:
Participants received nivolumab, 3 mg/kg, solution administered Intravenously (IV) every 2 weeks with placebo-matching dacarbazine solution administered IV every 3 weeks, until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
Participants received dacarbazine 1000 mg/m^2, solution administered IV every 3 weeks with placebo-matching nivolumab solution administered IV every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
Overall Number of Participants Analyzed 210 208
Median (95% Confidence Interval)
Unit of Measure: Months
5.06
(3.48 to 10.81)
2.17
(2.10 to 2.40)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine, Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Stratified Log Rank Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.43
Confidence Interval (2-Sided) 95%
0.34 to 0.56
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Progression-free Survival (PFS) Rate
Hide Description The PFS rate at a time point is the estimated percentage of patients who have not progressed and are alive at that time point following randomization and is estimated using the Kaplan-Meier methodology.
Time Frame Tumor assessments beginning at 9 weeks following randomization and continuing every 6 weeks for the first year, then every 12 weeks thereafter until disease progression or death, assessed to 17 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized to receive treatment
Arm/Group Title Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab
Hide Arm/Group Description:
Participants received nivolumab, 3 mg/kg, solution administered Intravenously (IV) every 2 weeks with placebo-matching dacarbazine solution administered IV every 3 weeks, until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
Participants received dacarbazine 1000 mg/m^2, solution administered IV every 3 weeks with placebo-matching nivolumab solution administered IV every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
Overall Number of Participants Analyzed 210 208
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
At 6 months
48.0
(40.8 to 54.9)
18.5
(13.1 to 24.6)
At 12 months
41.8
(34.0 to 49.3)
NA [1] 
(NA to NA)
[1]
The 12-month PFS rate for the dacarbazine group was not produced, as all PFS times were less than 12 months
5.Secondary Outcome
Title Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST)
Hide Description ORR is defined as the percentage of participants with a best overall response of RECIST-defined complete response (CR) or partial response (PR) divided by the number of randomized participants in each treatment arm. RECIST, volume 1.1 for target lesions: CR=disappearance of all target lesions; PR=at least a 30% decrease in the sum of the longest dimension (LD) of target lesions, taking as reference the baseline sum LD; stable disease=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started; PD=at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions, and the sum LD must have an absolute increase of ≥5 mm.
Time Frame Tumor assessments beginning at 9 weeks following randomization and continuing every 6 weeks for the first year, then every 12 weeks thereafter until disease progression or death, assessed to 17 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized to receive treatment
Arm/Group Title Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab
Hide Arm/Group Description:
Participants received nivolumab, 3 mg/kg, solution administered Intravenously (IV) every 2 weeks with placebo-matching dacarbazine solution administered IV every 3 weeks, until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
Participants received dacarbazine 1000 mg/m^2, solution administered IV every 3 weeks with placebo-matching nivolumab solution administered IV every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
Overall Number of Participants Analyzed 210 208
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
40
(33.3 to 47.0)
13.9
(9.5 to 19.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine, Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.06
Confidence Interval (2-Sided) 95%
2.52 to 6.54
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Overall Survival by Programmed Cell Death Ligand 1 (PD-L1) Expression Level
Hide Description Overall Survival by PD-L1 expression level, which was defined as the percent of tumor cells demonstrating plasma membrane PD-L1-staining in a minimum of 100 evaluable tumor cells per a Dako PD-L1 IHC assay (referred to as quantifiable PD-L1 expression). Assessment of OS by PD-L1 expression as measured by a validated assay and comparing OS in patients with tumor PD-L1 expression ≥5% versus patients with tumor PD-L1 expression <5%. Tumor tissue samples for PD-L1 testing were collected at screening from metastatic or unresectable sites prior to randomization.
Time Frame From date of randomization to date of disease progression or death, as assessed to 17 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized to receive treatment
Arm/Group Title Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab
Hide Arm/Group Description:
Participants received nivolumab, 3 mg/kg, solution administered Intravenously (IV) every 2 weeks with placebo-matching dacarbazine solution administered IV every 3 weeks, until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
Participants received dacarbazine 1000 mg/m^2, solution administered IV every 3 weeks with placebo-matching nivolumab solution administered IV every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
Overall Number of Participants Analyzed 210 208
Median (95% Confidence Interval)
Unit of Measure: Months
PD-L1 positive patients (n=59,61)
NA [1] 
(NA to NA)
9.56 [2] 
(6.21 to NA)
PD-L1 negative patients (n=127, 116)
NA [1] 
(NA to NA)
10.84
(8.34 to 13.96)
[1]
Not reached
[2]
The upper bound of the confidence interval was not reached because follow-up was insufficient
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine, Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Unstratified Hazard Ratio
Estimated Value 0.16
Confidence Interval (2-Sided) 95%
0.07 to 0.38
Estimation Comments PD-L1 positive group
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine, Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Unstratified Hazard Ratio
Estimated Value 0.56
Confidence Interval (2-Sided) 95%
0.37 to 0.85
Estimation Comments PD-L1 negative group
7.Secondary Outcome
Title Change From Baseline in Health-related Quality of Life (HRQoL) Scores
Hide Description HRQoL is evaluated by mean changes from baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) global health status/quality of life composite scale in all randomized patients. The QLQ-30 is a cancer-specific, self-administered questionnaire that contains 30 questions, covering global, functional, and symptom scales. Scores range from 0 to 100. Higher scores on global and functional scales indicate better quality of life (QoL), while higher scores on the symptom scales indicate declining QoL.
Time Frame At baseline and every 6 weeks for 12 months and at follow-up visits 1 and 2, assessed up to 17 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized to receive treatment; n=number of participants evaluable
Arm/Group Title Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab
Hide Arm/Group Description:
Participants received nivolumab, 3 mg/kg, solution administered Intravenously (IV) every 2 weeks with placebo-matching dacarbazine solution administered IV every 3 weeks, until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
Participants received dacarbazine 1000 mg/m^2, solution administered IV every 3 weeks with placebo-matching nivolumab solution administered IV every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
Overall Number of Participants Analyzed 210 208
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Week 7 (n=133, 125) 1.6  (19.55) 1.9  (19.69)
Week 13 (n=106, 60) 1.3  (18.90) 3.6  (16.97)
Week 19 (n=90, 41) 2.5  (17.24) 2.6  (16.40)
Week 25 (n=73, 31) 3.9  (20.03) -1.6  (20.35)
Week 31 (n=62, 17) 3.8  (19.01) 6.4  (17.81)
Week 37 (n=53, 9) 3.9  (18.96) 8.3  (20.83)
Week 43 (n=50, 6) 2.7  (19.01) -4.2  (19.54)
Week 49 (n=38, 4) 5.3  (20.45) 8.3  (9.62)
Week 55 (n=23, 2) 8.0  (22.26) -12.5  (5.89)
Week 61 (n=14, 1) 4.8  (23.05) 0.0 [1]   (NA)
Week 67 (n=6, 0) 1.4  (13.35) NA [2]   (NA)
Week 73 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
[1]
Sample size is too small to calculate standard deviation
[2]
No participants in this arm were available
8.Other Pre-specified Outcome
Title Number of Participants Who Died and With Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs) Leading to Discontinuation, Drug-related AEs Leading to Discontinuation, and Drug-related AEs
Hide Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=having certain, probable, possible, or unknown relationship to study drug.
Time Frame Day of first dose to day of final dose + 30 days, assessed up go 17 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug
Arm/Group Title Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab
Hide Arm/Group Description:
Participants received nivolumab, 3 mg/kg, solution administered Intravenously (IV) every 2 weeks with placebo-matching dacarbazine solution administered IV every 3 weeks, until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
Participants received dacarbazine 1000 mg/m^2, solution administered IV every 3 weeks with placebo-matching nivolumab solution administered IV every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
Overall Number of Participants Analyzed 206 205
Measure Type: Number
Unit of Measure: Participants
Deaths 47 96
SAEs 64 78
Drug-related SAEs 19 18
AEs leading to discontinuation 14 24
Drug-related AEs leading to discontinuation 5 7
Drug-related AEs 153 155
Time Frame Day of first dose to day of final dose + 30 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab
Hide Arm/Group Description Participants received nivolumab, 3 mg/kg, solution administered Intravenously (IV) every 2 weeks with placebo-matching dacarbazine solution administered IV every 3 weeks, until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion Participants received dacarbazine 1000 mg/m^2, solution administered IV every 3 weeks with placebo-matching nivolumab solution administered IV every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
All-Cause Mortality
Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab
Affected / at Risk (%) Affected / at Risk (%)
Total   64/206 (31.07%)   78/205 (38.05%) 
Blood and lymphatic system disorders     
Pancytopenia  1  0/206 (0.00%)  3/205 (1.46%) 
Thrombocytopenia  1  0/206 (0.00%)  3/205 (1.46%) 
Anaemia  1  1/206 (0.49%)  2/205 (0.98%) 
Neutropenia  1  0/206 (0.00%)  2/205 (0.98%) 
Cardiac disorders     
Atrial flutter  1  1/206 (0.49%)  0/205 (0.00%) 
Cardiac failure  1  1/206 (0.49%)  0/205 (0.00%) 
Tachycardia  1  0/206 (0.00%)  1/205 (0.49%) 
Atrial fibrillation  1  1/206 (0.49%)  1/205 (0.49%) 
Endocrine disorders     
Hypophysitis  1  1/206 (0.49%)  0/205 (0.00%) 
Hypopituitarism  1  1/206 (0.49%)  0/205 (0.00%) 
Eye disorders     
Diplopia  1  0/206 (0.00%)  1/205 (0.49%) 
Visual acuity reduced  1  0/206 (0.00%)  2/205 (0.98%) 
Eyelid retraction  1  0/206 (0.00%)  1/205 (0.49%) 
Gastrointestinal disorders     
Vomiting  1  2/206 (0.97%)  2/205 (0.98%) 
Nausea  1  0/206 (0.00%)  1/205 (0.49%) 
Abdominal pain  1  2/206 (0.97%)  2/205 (0.98%) 
Constipation  1  1/206 (0.49%)  0/205 (0.00%) 
Lower gastrointestinal haemorrhage  1  0/206 (0.00%)  1/205 (0.49%) 
Colitis  1  1/206 (0.49%)  0/205 (0.00%) 
Gastrointestinal disorder  1  0/206 (0.00%)  1/205 (0.49%) 
Ascites  1  1/206 (0.49%)  0/205 (0.00%) 
Gastric mucosal lesion  1  0/206 (0.00%)  1/205 (0.49%) 
Gastrointestinal haemorrhage  1  0/206 (0.00%)  1/205 (0.49%) 
Diarrhoea  1  2/206 (0.97%)  1/205 (0.49%) 
General disorders     
Death  1  0/206 (0.00%)  1/205 (0.49%) 
General physical health deterioration  1  3/206 (1.46%)  2/205 (0.98%) 
Oedema peripheral  1  0/206 (0.00%)  1/205 (0.49%) 
Non-cardiac chest pain  1  0/206 (0.00%)  1/205 (0.49%) 
Device dislocation  1  1/206 (0.49%)  0/205 (0.00%) 
Pain  1  2/206 (0.97%)  7/205 (3.41%) 
Chills  1  0/206 (0.00%)  1/205 (0.49%) 
Injection site reaction  1  0/206 (0.00%)  1/205 (0.49%) 
Infusion site reaction  1  0/206 (0.00%)  1/205 (0.49%) 
Pyrexia  1  4/206 (1.94%)  1/205 (0.49%) 
Fatigue  1  0/206 (0.00%)  2/205 (0.98%) 
Hepatobiliary disorders     
Cholelithiasis  1  1/206 (0.49%)  0/205 (0.00%) 
Jaundice  1  1/206 (0.49%)  0/205 (0.00%) 
Cholecystitis chronic  1  1/206 (0.49%)  0/205 (0.00%) 
Immune system disorders     
Hypersensitivity  1  2/206 (0.97%)  0/205 (0.00%) 
Infections and infestations     
Cellulitis  1  1/206 (0.49%)  1/205 (0.49%) 
Infection  1  0/206 (0.00%)  1/205 (0.49%) 
Lung infection  1  1/206 (0.49%)  0/205 (0.00%) 
Erysipelas  1  0/206 (0.00%)  1/205 (0.49%) 
Infusion site infection  1  0/206 (0.00%)  1/205 (0.49%) 
Skin infection  1  1/206 (0.49%)  0/205 (0.00%) 
Urinary tract infection  1  1/206 (0.49%)  0/205 (0.00%) 
Infected cyst  1  1/206 (0.49%)  0/205 (0.00%) 
Lower respiratory tract infection  1  1/206 (0.49%)  0/205 (0.00%) 
Pneumonia  1  1/206 (0.49%)  0/205 (0.00%) 
Injury, poisoning and procedural complications     
Infusion related reaction  1  2/206 (0.97%)  0/205 (0.00%) 
Lumbar vertebral fracture  1  1/206 (0.49%)  0/205 (0.00%) 
Post procedural complication  1  0/206 (0.00%)  1/205 (0.49%) 
Investigations     
General physical condition abnormal  1  2/206 (0.97%)  0/205 (0.00%) 
Pancreatic enzymes abnormal  1  1/206 (0.49%)  0/205 (0.00%) 
Metabolism and nutrition disorders     
Diabetic ketoacidosis  1  1/206 (0.49%)  0/205 (0.00%) 
Dehydration  1  0/206 (0.00%)  1/205 (0.49%) 
Hyperglycaemia  1  2/206 (0.97%)  1/205 (0.49%) 
Musculoskeletal and connective tissue disorders     
Muscular weakness  1  0/206 (0.00%)  2/205 (0.98%) 
Pathological fracture  1  1/206 (0.49%)  0/205 (0.00%) 
Bone pain  1  0/206 (0.00%)  2/205 (0.98%) 
Back pain  1  2/206 (0.97%)  1/205 (0.49%) 
Axillary mass  1  0/206 (0.00%)  1/205 (0.49%) 
Pain in extremity  1  0/206 (0.00%)  1/205 (0.49%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Metastases to central nervous system  1  2/206 (0.97%)  1/205 (0.49%) 
Metastases to liver  1  0/206 (0.00%)  1/205 (0.49%) 
Metastatic malignant melanoma  1  0/206 (0.00%)  2/205 (0.98%) 
Squamous cell carcinoma  1  1/206 (0.49%)  1/205 (0.49%) 
Squamous cell carcinoma of skin  1  1/206 (0.49%)  0/205 (0.00%) 
Malignant neoplasm progression  1  10/206 (4.85%)  17/205 (8.29%) 
Basal cell carcinoma  1  3/206 (1.46%)  0/205 (0.00%) 
Malignant melanoma  1  2/206 (0.97%)  4/205 (1.95%) 
Neoplasm  1  0/206 (0.00%)  1/205 (0.49%) 
Adenocarcinoma of colon  1  1/206 (0.49%)  0/205 (0.00%) 
Brain neoplasm  1  0/206 (0.00%)  1/205 (0.49%) 
Tumour pain  1  0/206 (0.00%)  1/205 (0.49%) 
Breast cancer  1  1/206 (0.49%)  0/205 (0.00%) 
Skin neoplasm bleeding  1  0/206 (0.00%)  1/205 (0.49%) 
Metastases to lymph nodes  1  1/206 (0.49%)  0/205 (0.00%) 
Nervous system disorders     
Disturbance in attention  1  0/206 (0.00%)  1/205 (0.49%) 
Muscle contractions involuntary  1  1/206 (0.49%)  0/205 (0.00%) 
Cognitive disorder  1  0/206 (0.00%)  1/205 (0.49%) 
Facial paresis  1  1/206 (0.49%)  0/205 (0.00%) 
Somnolence  1  0/206 (0.00%)  1/205 (0.49%) 
Dizziness  1  1/206 (0.49%)  0/205 (0.00%) 
Epilepsy  1  0/206 (0.00%)  1/205 (0.49%) 
Convulsion  1  1/206 (0.49%)  1/205 (0.49%) 
Presyncope  1  1/206 (0.49%)  1/205 (0.49%) 
Spinal cord compression  1  2/206 (0.97%)  2/205 (0.98%) 
Subarachnoid haemorrhage  1  1/206 (0.49%)  0/205 (0.00%) 
Guillain-Barre syndrome  1  1/206 (0.49%)  1/205 (0.49%) 
Pregnancy, puerperium and perinatal conditions     
Ectopic pregnancy  1  1/206 (0.49%)  0/205 (0.00%) 
Psychiatric disorders     
Confusional state  1  1/206 (0.49%)  1/205 (0.49%) 
Mania  1  0/206 (0.00%)  1/205 (0.49%) 
Renal and urinary disorders     
Renal failure acute  1  1/206 (0.49%)  1/205 (0.49%) 
Nephrolithiasis  1  0/206 (0.00%)  1/205 (0.49%) 
Haematuria  1  0/206 (0.00%)  1/205 (0.49%) 
Renal failure  1  0/206 (0.00%)  1/205 (0.49%) 
Renal injury  1  0/206 (0.00%)  1/205 (0.49%) 
Reproductive system and breast disorders     
Vaginal haemorrhage  1  1/206 (0.49%)  0/205 (0.00%) 
Genital haemorrhage  1  1/206 (0.49%)  0/205 (0.00%) 
Ovarian cyst  1  0/206 (0.00%)  1/205 (0.49%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  2/206 (0.97%)  0/205 (0.00%) 
Pulmonary embolism  1  0/206 (0.00%)  5/205 (2.44%) 
Respiratory distress  1  0/206 (0.00%)  1/205 (0.49%) 
Pleural effusion  1  0/206 (0.00%)  7/205 (3.41%) 
Respiratory failure  1  0/206 (0.00%)  2/205 (0.98%) 
Pneumonitis  1  2/206 (0.97%)  0/205 (0.00%) 
Epistaxis  1  0/206 (0.00%)  1/205 (0.49%) 
Haemoptysis  1  1/206 (0.49%)  0/205 (0.00%) 
Hypoxia  1  0/206 (0.00%)  1/205 (0.49%) 
Skin and subcutaneous tissue disorders     
Rash  1  1/206 (0.49%)  0/205 (0.00%) 
Rash maculo-papular  1  1/206 (0.49%)  0/205 (0.00%) 
Surgical and medical procedures     
Splenectomy  1  1/206 (0.49%)  0/205 (0.00%) 
Vascular disorders     
Hypertension  1  0/206 (0.00%)  1/205 (0.49%) 
Hypotension  1  0/206 (0.00%)  1/205 (0.49%) 
Thrombosis  1  1/206 (0.49%)  1/205 (0.49%) 
Haemorrhage  1  1/206 (0.49%)  0/205 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab
Affected / at Risk (%) Affected / at Risk (%)
Total   180/206 (87.38%)   177/205 (86.34%) 
Blood and lymphatic system disorders     
Thrombocytopenia  1  0/206 (0.00%)  21/205 (10.24%) 
Anaemia  1  19/206 (9.22%)  23/205 (11.22%) 
Neutropenia  1  0/206 (0.00%)  25/205 (12.20%) 
Endocrine disorders     
Hypothyroidism  1  13/206 (6.31%)  2/205 (0.98%) 
Gastrointestinal disorders     
Vomiting  1  23/206 (11.17%)  51/205 (24.88%) 
Nausea  1  48/206 (23.30%)  96/205 (46.83%) 
Abdominal pain  1  16/206 (7.77%)  17/205 (8.29%) 
Constipation  1  49/206 (23.79%)  53/205 (25.85%) 
Diarrhoea  1  50/206 (24.27%)  44/205 (21.46%) 
General disorders     
Oedema peripheral  1  17/206 (8.25%)  5/205 (2.44%) 
Pain  1  12/206 (5.83%)  8/205 (3.90%) 
Pyrexia  1  26/206 (12.62%)  18/205 (8.78%) 
Asthenia  1  36/206 (17.48%)  32/205 (15.61%) 
Fatigue  1  65/206 (31.55%)  50/205 (24.39%) 
Infections and infestations     
Nasopharyngitis  1  21/206 (10.19%)  6/205 (2.93%) 
Investigations     
Alanine aminotransferase increased  1  11/206 (5.34%)  6/205 (2.93%) 
Metabolism and nutrition disorders     
Decreased appetite  1  27/206 (13.11%)  29/205 (14.15%) 
Musculoskeletal and connective tissue disorders     
Myalgia  1  13/206 (6.31%)  8/205 (3.90%) 
Back pain  1  24/206 (11.65%)  18/205 (8.78%) 
Arthralgia  1  22/206 (10.68%)  15/205 (7.32%) 
Pain in extremity  1  25/206 (12.14%)  16/205 (7.80%) 
Musculoskeletal pain  1  13/206 (6.31%)  7/205 (3.41%) 
Nervous system disorders     
Dizziness  1  9/206 (4.37%)  12/205 (5.85%) 
Headache  1  31/206 (15.05%)  28/205 (13.66%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  15/206 (7.28%)  23/205 (11.22%) 
Cough  1  24/206 (11.65%)  24/205 (11.71%) 
Skin and subcutaneous tissue disorders     
Vitiligo  1  22/206 (10.68%)  1/205 (0.49%) 
Dry skin  1  15/206 (7.28%)  3/205 (1.46%) 
Photosensitivity reaction  1  4/206 (1.94%)  13/205 (6.34%) 
Rash  1  46/206 (22.33%)  16/205 (7.80%) 
Erythema  1  21/206 (10.19%)  6/205 (2.93%) 
Pruritus  1  46/206 (22.33%)  24/205 (11.71%) 
Vascular disorders     
Hypertension  1  14/206 (6.80%)  4/205 (1.95%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
An independent data monitoring committee (DMC) found that data from a DMC-requested database lock showed clear survival benefit with nivolumab and thus recommended unblinding the study and switching patients randomized to dacarbazine to nivolumab.
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
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01721772     History of Changes
Other Study ID Numbers: CA209-066
2012‐003718‐16 ( EudraCT Number )
First Submitted: November 2, 2012
First Posted: November 6, 2012
Results First Submitted: November 20, 2015
Results First Posted: February 25, 2016
Last Update Posted: August 8, 2018