Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Randomized Open-Label Phase 3 Trial of BMS-936558 (Nivolumab) Versus Investigator's Choice in Advanced (Unresectable or Metastatic) Melanoma Patients Progressing Post Anti-CTLA-4 Therapy

    Summary
    EudraCT number
    		 2012-001828-35
    Trial protocol
    		 BE   NL   AT   GB   DE   ES   IT   DK  
    Global end of trial date
    29 Dec 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    03 Dec 2021
    First version publication date
    03 Dec 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CA209-037
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bristol-Myers Squibb
    Sponsor organisation address
    Chaussée de la Hulpe 185, Brussels, Belgium, 1170
    Public contact
    EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com
    Scientific contact
    Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    29 Dec 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Dec 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Assess efficacy of objective response rate (ORR) and overall survival (OS) of Nivolumab versus Investigator's Choice in Advanced Melanoma patients progressing post anti-CTLA-4 therapy
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    21 Dec 2012
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Efficacy
    Long term follow-up duration
    		 5 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Austria: 10
    Country: Number of subjects enrolled
    Belgium: 23
    Country: Number of subjects enrolled
    Brazil: 5
    Country: Number of subjects enrolled
    Canada: 23
    Country: Number of subjects enrolled
    Denmark: 11
    Country: Number of subjects enrolled
    France: 31
    Country: Number of subjects enrolled
    Germany: 48
    Country: Number of subjects enrolled
    Israel: 2
    Country: Number of subjects enrolled
    Italy: 32
    Country: Number of subjects enrolled
    Netherlands: 5
    Country: Number of subjects enrolled
    Spain: 5
    Country: Number of subjects enrolled
    Switzerland: 3
    Country: Number of subjects enrolled
    United Kingdom: 43
    Country: Number of subjects enrolled
    United States: 164
    Worldwide total number of subjects
    405
    EEA total number of subjects
    165
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    257
    From 65 to 84 years
    143
    85 years and over
    5

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 405 participants randomized and 370 treated.

    Period 1
    Period 1 title
    Pre-Treatment
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Nivolumab
    Arm description
    		 Nivolumab 3 mg/kg IV Q2W
    Arm type
    		 Experimental

    Investigational medicinal product name
    BMS-936558 (Nivolumab)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    3 mg/kg IV over 60 minutes Q2W

    Arm title
    		 Investigator\'s Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Arm description
    		 Dacarbazine: 1000 mg/m^2 IV over 30 to 60 minutes Q3W, or Carboplatin: Area under the concentration-time curve (AUC) 6 IV over 30 minutes Q3W, and Paclitaxel: 175 mg/m^2 IV over 180 minutes Q3W
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Dacarbazine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for intravesical solution/solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    1000 mg/m^2 IV Q3W

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    175 mg/m^2 IV over 180 minutes Q3W

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Area under the concentration-time curve (AUC) 6 IV over 30 minutes Q3W

    Number of subjects in period 1
    		Nivolumab Investigator\'s Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Started
    272
    133
    Completed
    268
    102
    Not completed
    4
    31
         Consent withdrawn by subject
    1
    16
         Subject no longer met study criteria
    2
    2
         Subject request to discontinue Study treatment
    -
    13
         Poor/Non-compliance
    1
    -
    Period 2
    Period 2 title
    Treatment
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Nivolumab
    Arm description
    		 Nivolumab 3 mg/kg IV Q2W
    Arm type
    		 Experimental

    Investigational medicinal product name
    BMS-936558 (Nivolumab)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    3 mg/kg IV over 60 minutes Q2W

    Arm title
    		 Investigator\'s Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Arm description
    		 Dacarbazine: 1000 mg/m^2 IV over 30 to 60 minutes Q3W, or Carboplatin: Area under the concentration-time curve (AUC) 6 IV over 30 minutes Q3W, and Paclitaxel: 175 mg/m^2 IV over 180 minutes Q3W
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Dacarbazine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for intravesical solution/solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    1000 mg/m^2 IV Q3W

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    175 mg/m^2 IV over 180 minutes Q3W

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Area under the concentration-time curve (AUC) 6 IV over 30 minutes Q3W

    Number of subjects in period 2
    		Nivolumab Investigator\'s Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Started
    268
    102
    Completed
    0
    0
    Not completed
    268
    102
         Subject withdrew consent
    4
    2
         Maximum Clinical Benefit
    9
    3
         Subject no longer met study criteria
    4
    -
         Adverse Event unrelated to Study Drug
    6
    3
         Subject request to discontinue Study treatment
    26
    7
         Poor/Non-compliance
    2
    -
         Other reasons
    6
    2
         Study Drug Toxicity
    19
    11
         Disease Progression
    192
    74

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Nivolumab
    Reporting group description
    		 Nivolumab 3 mg/kg IV Q2W

    Reporting group title
    Investigator\'s Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Reporting group description
    		 Dacarbazine: 1000 mg/m^2 IV over 30 to 60 minutes Q3W, or Carboplatin: Area under the concentration-time curve (AUC) 6 IV over 30 minutes Q3W, and Paclitaxel: 175 mg/m^2 IV over 180 minutes Q3W

    Reporting group values
    		 Nivolumab Investigator\'s Choice (Dacarbazine or Carboplatin+Paclitaxel) Total
    Number of subjects
    		 272 133 405
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 177 80 257
        From 65-84 years
    		 91 52 143
        85 years and over
    		 4 1 5
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 58.7 ± 14.1 60.3 ± 12.4 -
    Sex: Female, Male
    Units:
        Female
    		 96 48 144
        Male
    		 176 85 261
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 269 129 398
        Black or African American
    		 1 2 3
        Asian
    		 2 0 2
        American Indian or Alaska Native
    		 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Other
    		 0 2 2
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 4 1 5
        Not Hispanic or Latino
    		 116 61 177
        Unknown or Not Reported
    		 152 71 223

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Nivolumab
    Reporting group description
    		 Nivolumab 3 mg/kg IV Q2W

    Reporting group title
    Investigator\'s Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Reporting group description
    		 Dacarbazine: 1000 mg/m^2 IV over 30 to 60 minutes Q3W, or Carboplatin: Area under the concentration-time curve (AUC) 6 IV over 30 minutes Q3W, and Paclitaxel: 175 mg/m^2 IV over 180 minutes Q3W
    Reporting group title
    Nivolumab
    Reporting group description
    		 Nivolumab 3 mg/kg IV Q2W

    Reporting group title
    Investigator\'s Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Reporting group description
    		 Dacarbazine: 1000 mg/m^2 IV over 30 to 60 minutes Q3W, or Carboplatin: Area under the concentration-time curve (AUC) 6 IV over 30 minutes Q3W, and Paclitaxel: 175 mg/m^2 IV over 180 minutes Q3W

    Primary: Objective Response Rate (ORR)

    		 Close Top of page
    End point title
    		 Objective Response Rate (ORR) [1]
    End point description
    Objective response rate (ORR) per Independent Review Committee (IRC) is defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of randomized participants using RECIST 1.1
    End point type
    Primary
    End point timeframe
    From date of randomization to the date of objectively documented progression, date of death, or the date of subsequent therapy (Up to approximately 38 months)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only summary statistics planned for this endpoint
    End point values
    		 Nivolumab Investigator\'s Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Number of subjects analysed
    272
    133
    Units: Percentage of participants
        number (confidence interval 95%)
    27.2 (22.0 to 32.9)
    9.8 (5.3 to 16.1)
    No statistical analyses for this end point

    Primary: Overall Survival (OS)

    		 Close Top of page
    End point title
    		 Overall Survival (OS)
    End point 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. Unit of measure (months) is the median survival time.
    End point type
    Primary
    End point timeframe
    Up to 96 months
    End point values
    		 Nivolumab Investigator\'s Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Number of subjects analysed
    272
    133
    Units: Months
        number (confidence interval 95%)
    15.74 (12.88 to 19.88)
    14.39 (11.66 to 18.17)
    Statistical analysis title
    		 Hazard Ratio (HR)
    Statistical analysis description
    Hazard Ratio is Nivolumab 3 mg/kg (IV) over Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Comparison groups
    Nivolumab v Investigator\'s Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Number of subjects included in analysis
    405
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [2]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 1.08
    Notes
    [2] - From stratified cox proportional hazard model with treatment group as a single covariate, stratified by BRAF status, prior anti-CTLA-4 benefit, and PD-L1 status (IVRS source)

    Secondary: Progression Free Survival (PFS)

    		 Close Top of page
    End point title
    		 Progression Free Survival (PFS)
    End point description
    Progression Free Survival (PFS) is defined as the time from randomization to the date of the first documented progression, as determined by the Independent Review Committee (IRC) using RECIST 1.1, or death due to any cause, whichever occurs first. Participants who died without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment prior to or on the date of initiation of the subsequent anti-cancer therapy. Unit of measure (months) is the median survival time.
    End point type
    Secondary
    End point timeframe
    From the date of randomization to the date of the first documented progression or death (Up to approximately 38 months)
    End point values
    		 Nivolumab Investigator\'s Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Number of subjects analysed
    272
    133
    Units: months
        number (confidence interval 95%)
    3.12 (2.33 to 3.52)
    3.65 (2.30 to 5.29)
    Statistical analysis title
    		 Hazard Ratio (HR)
    Statistical analysis description
    Hazard Ratio is Nivolumab 3 mg/kg (IV) over Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Comparison groups
    Nivolumab v Investigator\'s Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Number of subjects included in analysis
    405
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.03
    Confidence interval
         level
    		 95.1%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.36
    Notes
    [3] - From stratified cox proportional hazard model with treatment group as a single covariate, stratified by BRAF status, prior anti-CTLA-4 benefit, and PD-L1 status (IVRS source)

    Secondary: Objective Response Rate (ORR) by Baseline PD-L1 Expression

    		 Close Top of page
    End point title
    		 Objective Response Rate (ORR) by Baseline PD-L1 Expression
    End point description
    Objective Response Rate (ORR) is defined as the number of participants with a Best Overall Response (BOR) of complete response (CR) or partial response (PR) divided by number of randomized participants. PD-L1 expression evaluated for ORR.
    End point type
    Secondary
    End point timeframe
    From date of randomization to the date of objectively documented progression or the date of subsequent therapy (Up to approximately 38 months)
    End point values
    		 Nivolumab Investigator\'s Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Number of subjects analysed
    267 [4]
    131 [5]
    Units: Percentage of participants
    number (confidence interval 95%)
        <5% PD-L1 expression
    15.3 (9.7 to 22.5)
    13.8 (6.1 to 25.4)
        >=5% PD-L1 expression
    43.2 (33.9 to 53.0)
    12.2 (4.1 to 26.2)
    Notes
    [4] - <5% PD-L1 expression = 137 subjects >=5% PD-L1 expression = 111 subjects
    [5] - <5% PD-L1 expression = 58 subjects >=5% PD-L1 expression = 41 subjects
    Statistical analysis title
    		 Odds Ratio (OR)
    Statistical analysis description
    For <5% PD-L1 expression. Ratio of Nivolumab over Investigator's Choice
    Comparison groups
    Nivolumab v Investigator\'s Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Number of subjects included in analysis
    398
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [6]
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.44
         upper limit
    		 3.16
    Notes
    [6] - Subjects in this analysis are 137 from Nivolumab treatment and 58 from IC treatment
    Statistical analysis title
    		 Odds Ratio (OR)
    Statistical analysis description
    For >=5% PD-L1 expression. Ratio of Nivolumab over Investigator's Choice
    Comparison groups
    Nivolumab v Investigator\'s Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Number of subjects included in analysis
    398
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [7]
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    5.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.92
         upper limit
    		 19.08
    Notes
    [7] - Subjects in this analysis are 111 from Nivolumab treatment and 41 from IC treatment

    Secondary: Overall Survival (OS) by PD-L1 Expression

    		 Close Top of page
    End point title
    		 Overall Survival (OS) by PD-L1 Expression
    End point description
    Overall Survival (OS) by PD-L1 expression 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.
    End point type
    Secondary
    End point timeframe
    Up to 96 months
    End point values
    		 Nivolumab Investigator\'s Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Number of subjects analysed
    272 [8]
    133 [9]
    Units: Months
    median (confidence interval 95%)
        PD-L1 Positive
    31.44 (20.57 to 46.69)
    16.72 (11.83 to 31.44)
        PD-L1 Negative/Indeterminate
    11.14 (7.72 to 13.21)
    11.76 (8.05 to 17.81)
    Notes
    [8] - PD-L1 Positive = 135 PD-L1 Negative/Indeterminate = 137
    [9] - PD-L1 Positive = 67 PD-L1 Negative/Indeterminate = 66
    Statistical analysis title
    		 Hazard Ratio (HR)
    Statistical analysis description
    PD-L1 Positive
    Comparison groups
    Nivolumab v Investigator\'s Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Number of subjects included in analysis
    405
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [10]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 1.01
    Notes
    [10] - Subjects in this analysis are 135 from Nivolumab treatment and 67 from IC treatment
    Statistical analysis title
    		 Hazard Ratio (HR)
    Statistical analysis description
    PD-L1 Negative/Indeterminate
    Comparison groups
    Nivolumab v Investigator\'s Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Number of subjects included in analysis
    405
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [11]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.41
    Notes
    [11] - Subjects in this analysis are 137 from Nivolumab treatment and 66 from IC treatment

    Secondary: Mean change from baseline in Health-related Quality of Life (HRQoL)

    		 Close Top of page
    End point title
    		 Mean change from baseline in Health-related Quality of Life (HRQoL)
    End point 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 Increase from baseline indicates improvement in HRQoL. Lower scores for symptom scales=better HRQoL 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.
    End point type
    Secondary
    End point timeframe
    From Baseline (Day1) to second Follow-Up (Up to 96 months)
    End point values
    		 Nivolumab Investigator\'s Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Number of subjects analysed
    272
    133
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Physical Functioning Follow-Up 1
    -7.97 ± 20.49
    -12.73 ± 21.47
        Physical Functioning Follow-Up 2
    -3.66 ± 16.05
    -7.14 ± 16.02
        Role Functioning Follow-Up 1
    -14.94 ± 31.13
    -15.91 ± 29.76
        Role Functioning Follow-Up 2
    -7.80 ± 25.56
    -8.33 ± 21.52
        Emotional Functioning Follow-Up 1
    -5.09 ± 21.59
    -15.48 ± 24.48
        Emotional Functioning Follow-Up 2
    -0.94 ± 19.15
    -5.36 ± 25.98
        Cognitive Functioning Follow-Up 1
    -7.58 ± 16.79
    -7.94 ± 17.17
        Cognitive Functioning Follow-Up 2
    -3.49 ± 15.43
    -1.19 ± 13.55
        Social Functioning Follow-Up 1
    -8.66 ± 29.45
    -18.25 ± 26.82
        Social Functioning Follow-Up 2
    -1.61 ± 29.52
    -4.17 ± 24.69
        Global Health Status Follow-Up 1
    -8.23 ± 22.44
    -10.71 ± 17.71
        Global Health Status Follow-Up 2
    -1.61 ± 18.53
    -3.27 ± 12.07
        Dyspnea Follow-Up 1
    6.06 ± 27.96
    16.67 ± 24.67
        Dyspnea Follow-Up 2
    5.91 ± 22.20
    7.14 ± 24.61
        Insomnia Follow-Up 1
    3.46 ± 32.26
    0.00 ± 30.86
        Insomnia Follow-Up 2
    -4.84 ± 25.50
    0.00 ± 30.09
        Apatite loss Follow-Up 1
    6.93 ± 28.79
    13.64 ± 24.47
        Apatite loss Follow-Up 2
    5.91 ± 30.49
    2.38 ± 22.09
        Constipation Follow-Up 1
    7.36 ± 28.93
    0.00 ± 23.57
        Constipation Follow-Up 2
    2.15 ± 22.48
    -2.38 ± 29.99
        Diarrhea Follow-Up 1
    -0.43 ± 19.86
    6.35 ± 22.65
        Diarrhea Follow-Up 2
    1.08 ± 20.88
    1.19 ± 16.93
        Financial Difficulties Follow-Up 1
    -1.73 ± 25.87
    4.76 ± 39.84
        Financial Difficulties Follow-Up 2
    -1.08 ± 22.56
    -2.38 ± 28.59
        Fatigue Follow-Up 1
    8.95 ± 23.78
    15.66 ± 28.00
        Fatigue Follow-Up 2
    4.84 ± 22.55
    7.14 ± 21.85
        Nausea and Vomiting Follow-Up 1
    2.81 ± 17.19
    10.61 ± 25.48
        Nausea and Vomiting Follow-Up 2
    0.00 ± 15.39
    2.98 ± 18.73
        Pain Follow-Up 1
    6.06 ± 31.17
    6.82 ± 25.02
        Pain Follow-Up 2
    5.38 ± 24.84
    -1.79 ± 14.59
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    AEs and deaths collected were reported between first dose and 30 days after last dose of study therapy
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Investigator Choice (Dacarbazine or Carboplatin+Paclitaxel)
    Reporting group description
    		 Subjects with Advanced Unresectable Melanoma/Advanced Metastatic Melanoma were administered choice of either Dacarbazine at a dose of 1000 milligram/per square meter (mg/m2) IV between 30 to 60 minutes every 3 weeks (Q3W) or carboplatin (AUC 6) at a dose of 175 mg/m2 IV over 30 minutes and paclitaxel at a dose of 175 mg/m2 IV over 180 minutes Q3W until disease progression or treatment discontinuation or until end of the study treatment.

    Reporting group title
    BMS-936558A (Nivolumab)
    Reporting group description
    		 Subjects with Advanced Unresectable Melanoma/Advanced Metastatic Melanoma were administered BMS-936558A at a dose of 3 milligram/kilogram (mg/kg) intravenously (IV) over 60 minutes every 2 weeks (Q2W) until disease progression or unacceptable toxicity or until end of the study treatment.

    Serious adverse events
    		 Investigator Choice (Dacarbazine or Carboplatin+Paclitaxel) BMS-936558A (Nivolumab)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    24 / 102 (23.53%)
    162 / 268 (60.45%)
         number of deaths (all causes)
    3
    30
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    0 / 102 (0.00%)
    3 / 268 (1.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Keratoacanthoma
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    1 / 102 (0.98%)
    3 / 268 (1.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melanoma recurrent
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    5 / 102 (4.90%)
    39 / 268 (14.55%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 49
         deaths causally related to treatment / all
    0 / 4
    0 / 30
    Metastases to adrenals
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to pleura
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastatic malignant melanoma
         subjects affected / exposed
    0 / 102 (0.00%)
    5 / 268 (1.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Neoplasm malignant
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parathyroid tumour benign
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin neoplasm bleeding
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 268 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 102 (0.00%)
    4 / 268 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tonsil cancer
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour associated fever
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 268 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour pain
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour fistulisation
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 102 (0.98%)
    3 / 268 (1.12%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Peripheral embolism
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 268 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Superior vena cava syndrome
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    2 / 102 (1.96%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion site extravasation
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 102 (0.00%)
    4 / 268 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    1 / 102 (0.98%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic mass
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    2 / 102 (1.96%)
    4 / 268 (1.49%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ulcer
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    3 / 102 (2.94%)
    5 / 268 (1.87%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pleural effusion
         subjects affected / exposed
    1 / 102 (0.98%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Burnout syndrome
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    0 / 102 (0.00%)
    3 / 268 (1.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ejection fraction abnormal
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza B virus test positive
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver function test abnormal
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver function test increased
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative ileus
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Open fracture
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiation necrosis
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    1 / 102 (0.98%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular access site thrombosis
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 102 (0.00%)
    4 / 268 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Atrial flutter
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 102 (0.00%)
    3 / 268 (1.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac failure
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Myocardial infarction
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular arrhythmia
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Aphasia
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Autoimmune neuropathy
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain oedema
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Demyelination
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 268 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Status epilepticus
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Blood loss anaemia
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    2 / 102 (1.96%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    2 / 102 (1.96%)
    0 / 268 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Splenic haematoma
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 268 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Splenic lesion
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Retinal detachment
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 102 (0.00%)
    5 / 268 (1.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticular perforation
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    2 / 102 (1.96%)
    3 / 268 (1.12%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 102 (0.98%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 102 (0.00%)
    3 / 268 (1.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    3 / 102 (2.94%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic haemorrhage
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatocellular injury
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Skin haemorrhage
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 268 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 102 (1.96%)
    0 / 268 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tubulointerstitial nephritis
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal haemorrhage
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adrenal insufficiency
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypothyroidism
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 102 (0.98%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    2 / 102 (1.96%)
    6 / 268 (2.24%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Flank pain
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 268 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 102 (0.00%)
    4 / 268 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bacterial infection
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 102 (0.98%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 268 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 268 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 102 (0.00%)
    8 / 268 (2.99%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumonia pseudomonal
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 102 (0.00%)
    3 / 268 (1.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 102 (0.00%)
    3 / 268 (1.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular device infection
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 102 (0.00%)
    5 / 268 (1.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 102 (0.00%)
    2 / 268 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 102 (0.98%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 268 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Investigator Choice (Dacarbazine or Carboplatin+Paclitaxel) BMS-936558A (Nivolumab)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    97 / 102 (95.10%)
    258 / 268 (96.27%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    3 / 102 (2.94%)
    21 / 268 (7.84%)
         occurrences all number
    5
    61
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    9 / 102 (8.82%)
    34 / 268 (12.69%)
         occurrences all number
    21
    57
    Fatigue
         subjects affected / exposed
    50 / 102 (49.02%)
    132 / 268 (49.25%)
         occurrences all number
    78
    283
    Chills
         subjects affected / exposed
    3 / 102 (2.94%)
    18 / 268 (6.72%)
         occurrences all number
    3
    27
    Influenza like illness
         subjects affected / exposed
    4 / 102 (3.92%)
    17 / 268 (6.34%)
         occurrences all number
    6
    31
    Pain
         subjects affected / exposed
    3 / 102 (2.94%)
    27 / 268 (10.07%)
         occurrences all number
    3
    39
    Oedema peripheral
         subjects affected / exposed
    5 / 102 (4.90%)
    39 / 268 (14.55%)
         occurrences all number
    6
    53
    Pyrexia
         subjects affected / exposed
    9 / 102 (8.82%)
    51 / 268 (19.03%)
         occurrences all number
    11
    83
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    14 / 102 (13.73%)
    50 / 268 (18.66%)
         occurrences all number
    15
    69
    Cough
         subjects affected / exposed
    7 / 102 (6.86%)
    69 / 268 (25.75%)
         occurrences all number
    9
    105
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    6 / 102 (5.88%)
    33 / 268 (12.31%)
         occurrences all number
    7
    40
    Anxiety
         subjects affected / exposed
    1 / 102 (0.98%)
    19 / 268 (7.09%)
         occurrences all number
    1
    23
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    3 / 102 (2.94%)
    26 / 268 (9.70%)
         occurrences all number
    4
    52
    Blood creatinine increased
         subjects affected / exposed
    1 / 102 (0.98%)
    19 / 268 (7.09%)
         occurrences all number
    2
    44
    Blood alkaline phosphatase increased
         subjects affected / exposed
    3 / 102 (2.94%)
    21 / 268 (7.84%)
         occurrences all number
    8
    33
    Aspartate aminotransferase increased
         subjects affected / exposed
    5 / 102 (4.90%)
    36 / 268 (13.43%)
         occurrences all number
    6
    62
    Neutrophil count decreased
         subjects affected / exposed
    8 / 102 (7.84%)
    0 / 268 (0.00%)
         occurrences all number
    16
    0
    Platelet count decreased
         subjects affected / exposed
    9 / 102 (8.82%)
    9 / 268 (3.36%)
         occurrences all number
    26
    18
    White blood cell count decreased
         subjects affected / exposed
    9 / 102 (8.82%)
    6 / 268 (2.24%)
         occurrences all number
    28
    23
    Weight decreased
         subjects affected / exposed
    6 / 102 (5.88%)
    23 / 268 (8.58%)
         occurrences all number
    6
    34
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    9 / 102 (8.82%)
    3 / 268 (1.12%)
         occurrences all number
    26
    4
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    5 / 102 (4.90%)
    29 / 268 (10.82%)
         occurrences all number
    6
    40
    Headache
         subjects affected / exposed
    11 / 102 (10.78%)
    43 / 268 (16.04%)
         occurrences all number
    12
    68
    Paraesthesia
         subjects affected / exposed
    12 / 102 (11.76%)
    13 / 268 (4.85%)
         occurrences all number
    12
    15
    Neuropathy peripheral
         subjects affected / exposed
    11 / 102 (10.78%)
    10 / 268 (3.73%)
         occurrences all number
    17
    10
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    30 / 102 (29.41%)
    60 / 268 (22.39%)
         occurrences all number
    59
    160
    Neutropenia
         subjects affected / exposed
    23 / 102 (22.55%)
    3 / 268 (1.12%)
         occurrences all number
    44
    3
    Leukopenia
         subjects affected / exposed
    9 / 102 (8.82%)
    4 / 268 (1.49%)
         occurrences all number
    19
    5
    Thrombocytopenia
         subjects affected / exposed
    11 / 102 (10.78%)
    8 / 268 (2.99%)
         occurrences all number
    20
    13
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    10 / 102 (9.80%)
    49 / 268 (18.28%)
         occurrences all number
    11
    77
    Constipation
         subjects affected / exposed
    22 / 102 (21.57%)
    50 / 268 (18.66%)
         occurrences all number
    27
    79
    Abdominal pain upper
         subjects affected / exposed
    6 / 102 (5.88%)
    21 / 268 (7.84%)
         occurrences all number
    7
    30
    Dry mouth
         subjects affected / exposed
    2 / 102 (1.96%)
    14 / 268 (5.22%)
         occurrences all number
    2
    16
    Diarrhoea
         subjects affected / exposed
    18 / 102 (17.65%)
    84 / 268 (31.34%)
         occurrences all number
    28
    210
    Dyspepsia
         subjects affected / exposed
    3 / 102 (2.94%)
    21 / 268 (7.84%)
         occurrences all number
    5
    27
    Nausea
         subjects affected / exposed
    42 / 102 (41.18%)
    87 / 268 (32.46%)
         occurrences all number
    74
    121
    Vomiting
         subjects affected / exposed
    24 / 102 (23.53%)
    55 / 268 (20.52%)
         occurrences all number
    40
    76
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    2 / 102 (1.96%)
    22 / 268 (8.21%)
         occurrences all number
    2
    29
    Alopecia
         subjects affected / exposed
    29 / 102 (28.43%)
    8 / 268 (2.99%)
         occurrences all number
    36
    9
    Pruritus
         subjects affected / exposed
    2 / 102 (1.96%)
    71 / 268 (26.49%)
         occurrences all number
    2
    112
    Rash
         subjects affected / exposed
    5 / 102 (4.90%)
    56 / 268 (20.90%)
         occurrences all number
    6
    80
    Rash maculo-papular
         subjects affected / exposed
    2 / 102 (1.96%)
    21 / 268 (7.84%)
         occurrences all number
    2
    48
    Vitiligo
         subjects affected / exposed
    0 / 102 (0.00%)
    31 / 268 (11.57%)
         occurrences all number
    0
    36
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 102 (0.00%)
    25 / 268 (9.33%)
         occurrences all number
    0
    32
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    20 / 102 (19.61%)
    74 / 268 (27.61%)
         occurrences all number
    39
    151
    Muscle spasms
         subjects affected / exposed
    1 / 102 (0.98%)
    14 / 268 (5.22%)
         occurrences all number
    1
    18
    Back pain
         subjects affected / exposed
    0 / 102 (0.00%)
    54 / 268 (20.15%)
         occurrences all number
    0
    75
    Myalgia
         subjects affected / exposed
    10 / 102 (9.80%)
    30 / 268 (11.19%)
         occurrences all number
    24
    50
    Pain in extremity
         subjects affected / exposed
    11 / 102 (10.78%)
    36 / 268 (13.43%)
         occurrences all number
    15
    50
    Neck pain
         subjects affected / exposed
    2 / 102 (1.96%)
    15 / 268 (5.60%)
         occurrences all number
    2
    16
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    4 / 102 (3.92%)
    26 / 268 (9.70%)
         occurrences all number
    5
    35
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 102 (1.96%)
    24 / 268 (8.96%)
         occurrences all number
    2
    31
    Urinary tract infection
         subjects affected / exposed
    4 / 102 (3.92%)
    21 / 268 (7.84%)
         occurrences all number
    4
    33
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    20 / 102 (19.61%)
    52 / 268 (19.40%)
         occurrences all number
    25
    80
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 102 (0.00%)
    19 / 268 (7.09%)
         occurrences all number
    0
    37
    Hyponatraemia
         subjects affected / exposed
    1 / 102 (0.98%)
    23 / 268 (8.58%)
         occurrences all number
    1
    45
    Hypokalaemia
         subjects affected / exposed
    1 / 102 (0.98%)
    14 / 268 (5.22%)
         occurrences all number
    2
    29

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Mar 2013
    Update to Summary of Safety section to include new preliminary reproductive toxicology data that was distributed as a Non-clinical Expedited Safety Report and to include change to the guidance on contraception.
    29 Apr 2013
    Modified to expand the number of prior therapies allowed in the eligibility criteria.
    24 Oct 2013
    Updated the study design to allow an adequately powered statistical comparison of the co-primary endpoint of Objective Response Rate (ORR) at an earlier timepoint while maintaining the power for statistical comparison of the other co-primary endpoint of Overall Survival (OS).
    28 Mar 2014
    Modified the co-primary endpoint to allow a non-comparative estimation of ORR on the nivolumab arm. The OS co-primary endpoint will be tested using 4.9% significance level.
    05 Oct 2016
    Modifications to study design and duration. Modifications to Inclusion Criteria. Modifications to treatment duration and dosing calculating. Modification to discontinuation criteria. Modifications to safety assessments.
    27 Jan 2017
    Modification to Arm A (Nivolumab) Follow-up assessments.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun Apr 28 22:50:59 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA