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    Clinical Trial Results:
    A DOSE FREQUENCY OPTIMIZATION, PHASE IIIB/IV TRIAL OF NIVOLUMAB 240 MG EVERY 2 WEEKS VS NIVOLUMAB 480 MG EVERY 4 WEEKS IN SUBJECTS WITH ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER WHO RECEIVED UP TO 12 MONTHS OF NIVOLUMAB AT 3 MG/KG OR 240 MG EVERY 2 WEEKS

    Summary
    EudraCT number
    		 2015-004633-27
    Trial protocol
    		 DE   IE   AT   ES   IT   FR  
    Global end of trial date
    18 Feb 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    03 Feb 2023
    First version publication date
    03 Feb 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CA209-384
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02713867
    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
    22 Feb 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Feb 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The coprimary objectives are to compare the PFS rate at 6 months after randomization and PFS rate at 1 year after randomization, as measured by investigator-assessed response using Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 criteria, of nivolumab 3 mg/kg every 2 weeks (Arm 1) and nivolumab 6 mg/kg every 4 weeks (Arm 2) in subjects with advanced/metastatic (Stage IIIb/IV) NSCLC (non-Sq and Sq).
    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 Apr 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 21
    Country: Number of subjects enrolled
    Canada: 7
    Country: Number of subjects enrolled
    France: 108
    Country: Number of subjects enrolled
    Germany: 44
    Country: Number of subjects enrolled
    Italy: 25
    Country: Number of subjects enrolled
    Spain: 31
    Country: Number of subjects enrolled
    United States: 127
    Worldwide total number of subjects
    363
    EEA total number of subjects
    208
    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)
    143
    From 65 to 84 years
    213
    85 years and over
    7

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 363 Randomized, 358 Treated

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Nivolumab 480mg
    Arm description
    		 Nivolumab 480mg Q4W
    Arm type
    		 Experimental

    Investigational medicinal product name
    nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravascular use
    Dosage and administration details
    480mg Q4W

    Arm title
    		 Nivolumab 240mg
    Arm description
    		 Nivolumab 240mg Q2W
    Arm type
    		 Experimental

    Investigational medicinal product name
    nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravascular use
    Dosage and administration details
    240mg Q2W

    Number of subjects in period 1
    		Nivolumab 480mg Nivolumab 240mg
    Started
    180
    183
    Completed
    178
    180
    Not completed
    2
    3
         Other Reason
    2
    1
         Participant Withdrew consent
    -
    2
    Period 2
    Period 2 title
    Treatment Period
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Nivolumab 480mg
    Arm description
    		 Nivolumab 480mg Q4W
    Arm type
    		 Experimental

    Investigational medicinal product name
    nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravascular use
    Dosage and administration details
    480mg Q4W

    Arm title
    		 Nivolumab 240mg
    Arm description
    		 Nivolumab 240mg Q2W
    Arm type
    		 Experimental

    Investigational medicinal product name
    nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravascular use
    Dosage and administration details
    240mg Q2W

    Number of subjects in period 2
    		Nivolumab 480mg Nivolumab 240mg
    Started
    178
    180
    Completed
    0
    0
    Not completed
    178
    180
         Adverse event, serious fatal
    7
    3
         Requested to Discontinue
    8
    8
         Other Reasons
    22
    28
         Poor/Non Compliance
    1
    -
         Maximum Clinical Benefit
    5
    6
         No longer meets study criteria
    2
    1
         Study Drug Toxicity
    16
    19
         Withdrew consent
    3
    6
         AE unrelated to Study Drug
    11
    10
         Disease Progression
    82
    83
         Administrative reason by sponsor
    21
    16

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Nivolumab 480mg
    Reporting group description
    		 Nivolumab 480mg Q4W

    Reporting group title
    Nivolumab 240mg
    Reporting group description
    		 Nivolumab 240mg Q2W

    Reporting group values
    		 Nivolumab 480mg Nivolumab 240mg Total
    Number of subjects
    		 180 183 363
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 75 68 143
        From 65-84 years
    		 100 113 213
        85 years and over
    		 5 2 7
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 66.4 ± 9.25 66.5 ± 8.65 -
    Sex: Female, Male
    Units: Participants
        Female
    		 49 54 103
        Male
    		 131 129 260
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 1 3 4
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 8 8 16
        White
    		 169 167 336
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 2 5 7
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 3 4 7
        Not Hispanic or Latino
    		 118 115 233
        Unknown or Not Reported
    		 59 64 123

    End points

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    End points reporting groups
    Reporting group title
    Nivolumab 480mg
    Reporting group description
    		 Nivolumab 480mg Q4W

    Reporting group title
    Nivolumab 240mg
    Reporting group description
    		 Nivolumab 240mg Q2W
    Reporting group title
    Nivolumab 480mg
    Reporting group description
    		 Nivolumab 480mg Q4W

    Reporting group title
    Nivolumab 240mg
    Reporting group description
    		 Nivolumab 240mg Q2W

    Primary: Progression Free Survival Rate (PFSR) at 12 Months

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    End point title
    		 Progression Free Survival Rate (PFSR) at 12 Months [1]
    End point description
    The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: the appearance of one or more new lesions is also considered progression.
    End point type
    Primary
    End point timeframe
    At 12 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: No Statistical Analysis done for this endpoint
    End point values
    		 Nivolumab 480mg Nivolumab 240mg
    Number of subjects analysed
    180
    183
    Units: Proportion of Participants
        number (confidence interval 95%)
    0.53 (0.46 to 0.61)
    0.55 (0.47 to 0.62)
    No statistical analyses for this end point

    Primary: Progression Free Survival Rate (PFSR) at 6 Months

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    End point title
    		 Progression Free Survival Rate (PFSR) at 6 Months [2]
    End point description
    The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: the appearance of one or more new lesions is also considered progression.
    End point type
    Primary
    End point timeframe
    At 6 Months
    Notes
    [2] - 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: No Statistical Analysis done for this endpoint
    End point values
    		 Nivolumab 480mg Nivolumab 240mg
    Number of subjects analysed
    180
    183
    Units: Proportion of Participants
        number (confidence interval 95%)
    0.76 (0.70 to 0.83)
    0.79 (0.73 to 0.85)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with an Adverse Events (AEs)

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    End point title
    		 Percentage of Participants with an Adverse Events (AEs)
    End point description
    Percentage of participants with an Adverse Event due to any cause An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.
    End point type
    Secondary
    End point timeframe
    Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
    End point values
    		 Nivolumab 480mg Nivolumab 240mg
    Number of subjects analysed
    178
    180
    Units: Percentage of Participants
        number (not applicable)
    91.6
    97.8
    No statistical analyses for this end point

    Secondary: Percentage of Participants with an Serious Adverse Events (SAEs)

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    End point title
    		 Percentage of Participants with an Serious Adverse Events (SAEs)
    End point description
    Percentage of participants with an Serious Adverse Event due to any cause. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: 1)results in death 2) is life-threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe) 3) requires inpatient hospitalization or causes prolongation of existing hospitalization 4) results in persistent or significant disability/incapacity 5) is a congenital anomaly/birth defect 6) is an important medical event (defined as a medical event(s) that may not be immediately life-threatening or result in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the participant or may require intervention [eg, medical, surgical] to prevent one of the other serious outcomes listed in the definition above.)
    End point type
    Secondary
    End point timeframe
    Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
    End point values
    		 Nivolumab 480mg Nivolumab 240mg
    Number of subjects analysed
    178
    180
    Units: Percentage of Participants
        number (not applicable)
    34.8
    39.4
    No statistical analyses for this end point

    Secondary: Percentage of Participants with an Adverse Events Leading to Discontinuation (AEsDC)

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    End point title
    		 Percentage of Participants with an Adverse Events Leading to Discontinuation (AEsDC)
    End point description
    Percentage of Participants with an Adverse Event leading to discontinuation (AEsDC) due to any cause. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.
    End point type
    Secondary
    End point timeframe
    Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
    End point values
    		 Nivolumab 480mg Nivolumab 240mg
    Number of subjects analysed
    178
    180
    Units: Percentage of Participants
        number (not applicable)
    19.1
    17.8
    No statistical analyses for this end point

    Secondary: Percentage of Participants with an Immune Mediated Adverse Events (IMAEs)

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    End point title
    		 Percentage of Participants with an Immune Mediated Adverse Events (IMAEs)
    End point description
    Percentage of Participants with an Immune Mediated Adverse Events treated with Immune-Modulating Medication
    End point type
    Secondary
    End point timeframe
    Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
    End point values
    		 Nivolumab 480mg Nivolumab 240mg
    Number of subjects analysed
    178
    180
    Units: Percentage of Participants
    number (not applicable)
        Diarrhea/Colitis
    3.4
    5.0
        Hepatitis
    0.0
    1.7
        Pneumonitis
    3.4
    3.3
        Nephritis and Renal Dysfunction
    0.6
    0.0
        Rash
    7.3
    7.2
        Hypersensitivity/Infusion Reaction
    0.0
    0.0
    No statistical analyses for this end point

    Secondary: Percentage of Participants with an Select Adverse Events

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    End point title
    		 Percentage of Participants with an Select Adverse Events
    End point description
    Percentage of Participants with an Select Adverse Event due to any cause Select adverse events include adverse events in the following systems: Gastrointestinal, Hepatic, Pulmonary, Renal, Skin, Hypersensitivity/Infusion reaction and Endrocrine.
    End point type
    Secondary
    End point timeframe
    Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
    End point values
    		 Nivolumab 480mg Nivolumab 240mg
    Number of subjects analysed
    178
    180
    Units: Percentage of Participants
    number (not applicable)
        Gastrointestinal
    18.5
    25.0
        Hepatic
    2.2
    10.0
        Pulmonary
    6.7
    5.0
        Renal
    10.1
    5.6
        Skin
    30.9
    33.9
        Hypersensitivity/Infusion Reaction
    0.0
    1.1
        Endocrine
    16.3
    18.3
    No statistical analyses for this end point

    Secondary: Percentage of Participants with an Event of Special Interest (ESI)

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    End point title
    		 Percentage of Participants with an Event of Special Interest (ESI)
    End point description
    Other ESI included the following categories: demyelination, encephalitis, Guillain-Barré syndrome (GBS), myasthenic syndrome, pancreatitis, uveitis, myositis, myocarditis, rhabdomyolysis, and Graft Versus Host Disease (GVHD).
    End point type
    Secondary
    End point timeframe
    Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
    End point values
    		 Nivolumab 480mg Nivolumab 240mg
    Number of subjects analysed
    178
    180
    Units: Percentage of Participants
    number (not applicable)
        Pancreatitis
    1.1
    2.8
        demyelination
    0
    0
        encephalitis
    0
    0
        GBS
    0
    0
        myasthenic syndrome
    0
    0
        uveitis
    0
    0
        myositis
    0
    0
        myocarditis
    0
    0
        rhabdomyolysis
    0
    0
        GVHD
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants with Laboratory Test Abnormalities

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    End point title
    		 Number of Participants with Laboratory Test Abnormalities
    End point description
    Number of participants with any laboratory test result that is clinically significant or meets the definition of an SAE (Grade 3+4 combined)
    End point type
    Secondary
    End point timeframe
    Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
    End point values
    		 Nivolumab 480mg Nivolumab 240mg
    Number of subjects analysed
    178
    180
    Units: Number of Participants
        Alanine Aminotransferase
    1
    1
        Alkaline Phosphate
    1
    0
        Aspartate Aminotransferase
    1
    2
        Bilirubin, Total
    1
    1
        Creatinine
    1
    2
        Hemoglobin
    0
    4
        Hypercalcemia
    2
    5
        Hyperkalemia
    4
    3
        Hypermagnesemia
    4
    5
        Hypernatremia
    0
    0
        Hypocalcemia
    4
    6
        Hypokalemia
    3
    6
        Hypomagnesemia
    3
    2
        Hypnatremia
    6
    7
        Leukocytes
    1
    3
        Lymphocytes
    22
    21
        Neutrophils
    3
    4
        Platelet Count
    3
    1
    No statistical analyses for this end point

    Secondary: Progression Free Survival Rate (PFSR) at 24 Months

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    End point title
    		 Progression Free Survival Rate (PFSR) at 24 Months
    End point description
    The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: the appearance of one or more new lesions is also considered progression.
    End point type
    Secondary
    End point timeframe
    At 24 Months
    End point values
    		 Nivolumab 480mg Nivolumab 240mg
    Number of subjects analysed
    180
    183
    Units: Proportion of Participants
        number (confidence interval 95%)
    0.34 (0.27 to 0.42)
    0.35 (0.28 to 0.43)
    No statistical analyses for this end point

    Secondary: Progression Free Survival Rate (PFSR) by Tumor Histology at 12 Months

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    End point title
    		 Progression Free Survival Rate (PFSR) by Tumor Histology at 12 Months
    End point description
    The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: the appearance of one or more new lesions is also considered progression.
    End point type
    Secondary
    End point timeframe
    At 12 Months
    End point values
    		 Nivolumab 480mg Nivolumab 240mg
    Number of subjects analysed
    180
    183
    Units: Proportion of Participants
    number (confidence interval 95%)
        Squamous
    0.50 (0.37 to 0.64)
    0.42 (0.29 to 0.55)
        Non Squamous
    0.54 (0.45 to 0.63)
    0.60 (0.51 to 0.70)
    No statistical analyses for this end point

    Secondary: Progression Free Survival Rate (PFSR) by Response Criteria at 12 Months

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    End point title
    		 Progression Free Survival Rate (PFSR) by Response Criteria at 12 Months
    End point description
    The proportion of participants remaining progression free and surviving at 12 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
    End point type
    Secondary
    End point timeframe
    At 12 Months
    End point values
    		 Nivolumab 480mg Nivolumab 240mg
    Number of subjects analysed
    180
    183
    Units: Proportion of Participants
    number (confidence interval 95%)
        Complete Remission (CR)/Partial Remission (PR)
    0.63 (0.51 to 0.75)
    0.66 (0.53 to 0.78)
        Stable Disease (SD)
    0.47 (0.38 to 0.57)
    0.48 (0.39 to 0.58)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS) Rate at 12 Months

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    End point title
    		 Overall Survival (OS) Rate at 12 Months
    End point description
    The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive.
    End point type
    Secondary
    End point timeframe
    At 12 Months
    End point values
    		 Nivolumab 480mg Nivolumab 240mg
    Number of subjects analysed
    142
    150
    Units: Proportion of participants
        number (confidence interval 95%)
    0.851 (0.799 to 0.902)
    0.908 (0.866 to 0.951)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS) Rate up to 60 Months

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    End point title
    		 Overall Survival (OS) Rate up to 60 Months
    End point description
    The proportion of participants alive up to 60 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive. Here "99999" means NA
    End point type
    Secondary
    End point timeframe
    From randomization to the date of death, Up to 60 Months
    End point values
    		 Nivolumab 480mg Nivolumab 240mg
    Number of subjects analysed
    180
    183
    Units: Proportion of participants
    number (confidence interval 95%)
        12 Months
    0.82 (0.76 to 0.88)
    0.88 (0.83 to 0.93)
        24 Months
    0.62 (0.55 to 0.69)
    0.70 (0.63 to 0.77)
        36 Months
    0.49 (0.42 to 0.57)
    0.57 (0.49 to 0.64)
        48 Months
    99999 (99999 to 99999)
    99999 (99999 to 99999)
        60 Months
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Overall Survival Rate by Histology at 12 Months

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    End point title
    		 Overall Survival Rate by Histology at 12 Months
    End point description
    The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive. OS rate by histology did not have data collected after 12 months randomization.
    End point type
    Secondary
    End point timeframe
    at 12 Months
    End point values
    		 Nivolumab 480mg Nivolumab 240mg
    Number of subjects analysed
    180
    183
    Units: Proportion of participants
    number (confidence interval 95%)
        Squamous
    0.74 (0.63 to 0.85)
    0.80 (0.70 to 0.90)
        Non Squamous
    0.86 (0.80 to 0.92)
    0.92 (0.87 to 0.97)
    No statistical analyses for this end point

    Secondary: Overall Survival Rate by Response Criteria at 12 Months

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    End point title
    		 Overall Survival Rate by Response Criteria at 12 Months
    End point description
    The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. OS rate by response did not have data collected after 12 months randomization.
    End point type
    Secondary
    End point timeframe
    12 Months
    End point values
    		 Nivolumab 480mg Nivolumab 240mg
    Number of subjects analysed
    180
    183
    Units: Proportion of participants
    number (confidence interval 95%)
        CR/PR
    0.90 (0.82 to 0.98)
    0.93 (0.87 to 1.00)
        SD
    0.78 (0.70 to 0.86)
    0.85 (0.78 to 0.92)
    No statistical analyses for this end point

    Secondary: Percentage of participants who experienced eeath

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    End point title
    		 Percentage of participants who experienced eeath
    End point description
    Percentage of Participants who experienced Death due to any cause
    End point type
    Secondary
    End point timeframe
    Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
    End point values
    		 Nivolumab 480mg Nivolumab 240mg
    Number of subjects analysed
    178
    180
    Units: Percentage of Participants
        number (not applicable)
    49.4
    43.9
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events and SAEs: between first dose and 100 days after last dose of study therapy (Approximately 16 months up to 56 months). All Cause Mortality, from randomization to study completion.: Approximately 5 years and 8 months.
    Adverse event reporting additional description
    The number at Risk for All-Cause Mortality represents all Randomized Participants to study completion. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication" or similar.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    NIVOLUMAB 240 mg Q2W
    Reporting group description
    		 Nivolumab 240mg Q2W

    Reporting group title
    NIVOLUMAB 480 mg Q4W
    Reporting group description
    		 Nivolumab 480mg Q4W

    Serious adverse events
    		 NIVOLUMAB 240 mg Q2W NIVOLUMAB 480 mg Q4W
    Total subjects affected by serious adverse events
         subjects affected / exposed
    78 / 180 (43.33%)
    80 / 178 (44.94%)
         number of deaths (all causes)
    79
    88
         number of deaths resulting from adverse events
    15
    21
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Laryngeal cancer
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glottis carcinoma
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         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
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         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
    14 / 180 (7.78%)
    10 / 178 (5.62%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 10
         deaths causally related to treatment / all
    0 / 8
    0 / 8
    Metastases to central nervous system
         subjects affected / exposed
    2 / 180 (1.11%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal adenocarcinoma
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cancer
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         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 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leriche syndrome
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         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
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drowning
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Fatigue
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pain
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pyrexia
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 180 (0.00%)
    2 / 178 (1.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Reproductive system and breast disorders
    Acquired phimosis
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         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
    Acute respiratory failure
         subjects affected / exposed
    2 / 180 (1.11%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    4 / 180 (2.22%)
    11 / 178 (6.18%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Dyspnoea
         subjects affected / exposed
    2 / 180 (1.11%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 180 (0.00%)
    2 / 178 (1.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Immune-mediated lung disease
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    4 / 180 (2.22%)
    4 / 178 (2.25%)
         occurrences causally related to treatment / all
    3 / 4
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Organising pneumonia
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    4 / 180 (2.22%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haematuria
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 180 (0.56%)
    2 / 178 (1.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         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 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Spinal compression fracture
         subjects affected / exposed
    2 / 180 (1.11%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound evisceration
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         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 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac failure
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    2 / 180 (1.11%)
    2 / 178 (1.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Carotid artery occlusion
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Cerebral ischaemia
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nystagmus
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    2 / 180 (1.11%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         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
    Anaemia
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Autoimmune colitis
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 180 (0.56%)
    4 / 178 (2.25%)
         occurrences causally related to treatment / all
    1 / 1
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal pain
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         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 / 180 (0.00%)
    2 / 178 (1.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 180 (0.00%)
    2 / 178 (1.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colonic fistula
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Subcapsular renal haematoma
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypophysitis
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypopituitarism
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         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
    Arthritis
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    1 / 180 (0.56%)
    2 / 178 (1.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoporosis
         subjects affected / exposed
    2 / 180 (1.11%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polymyalgia rheumatica
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Soft tissue disorder
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal pain
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thoracic spinal stenosis
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         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 / 180 (0.00%)
    2 / 178 (1.12%)
         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 / 180 (0.00%)
    1 / 178 (0.56%)
         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
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         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
    3 / 180 (1.67%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung abscess
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Medical device site cellulitis
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    10 / 180 (5.56%)
    8 / 178 (4.49%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 8
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Pneumonia bacterial
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Sepsis
         subjects affected / exposed
    3 / 180 (1.67%)
    5 / 178 (2.81%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    2 / 180 (1.11%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection bacterial
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         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
    1 / 180 (0.56%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural sepsis
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 180 (0.56%)
    2 / 178 (1.12%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hyperkalaemia
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 178 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 178 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 NIVOLUMAB 240 mg Q2W NIVOLUMAB 480 mg Q4W
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    169 / 180 (93.89%)
    146 / 178 (82.02%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    13 / 180 (7.22%)
    11 / 178 (6.18%)
         occurrences all number
    17
    12
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    26 / 180 (14.44%)
    27 / 178 (15.17%)
         occurrences all number
    34
    31
    Fatigue
         subjects affected / exposed
    40 / 180 (22.22%)
    29 / 178 (16.29%)
         occurrences all number
    48
    34
    Non-cardiac chest pain
         subjects affected / exposed
    10 / 180 (5.56%)
    5 / 178 (2.81%)
         occurrences all number
    11
    7
    Pyrexia
         subjects affected / exposed
    16 / 180 (8.89%)
    17 / 178 (9.55%)
         occurrences all number
    20
    20
    Oedema peripheral
         subjects affected / exposed
    15 / 180 (8.33%)
    14 / 178 (7.87%)
         occurrences all number
    18
    14
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    12 / 180 (6.67%)
    8 / 178 (4.49%)
         occurrences all number
    13
    8
    Cough
         subjects affected / exposed
    36 / 180 (20.00%)
    25 / 178 (14.04%)
         occurrences all number
    44
    31
    Dyspnoea
         subjects affected / exposed
    26 / 180 (14.44%)
    23 / 178 (12.92%)
         occurrences all number
    28
    26
    Pneumonitis
         subjects affected / exposed
    7 / 180 (3.89%)
    10 / 178 (5.62%)
         occurrences all number
    8
    10
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    21 / 180 (11.67%)
    8 / 178 (4.49%)
         occurrences all number
    22
    8
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    7 / 180 (3.89%)
    14 / 178 (7.87%)
         occurrences all number
    10
    15
    Lipase increased
         subjects affected / exposed
    14 / 180 (7.78%)
    8 / 178 (4.49%)
         occurrences all number
    21
    11
    Weight decreased
         subjects affected / exposed
    20 / 180 (11.11%)
    9 / 178 (5.06%)
         occurrences all number
    23
    9
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    10 / 180 (5.56%)
    10 / 178 (5.62%)
         occurrences all number
    14
    12
    Nervous system disorders
    Headache
         subjects affected / exposed
    16 / 180 (8.89%)
    14 / 178 (7.87%)
         occurrences all number
    16
    17
    Dizziness
         subjects affected / exposed
    17 / 180 (9.44%)
    6 / 178 (3.37%)
         occurrences all number
    22
    6
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    20 / 180 (11.11%)
    12 / 178 (6.74%)
         occurrences all number
    30
    15
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    7 / 180 (3.89%)
    11 / 178 (6.18%)
         occurrences all number
    7
    12
    Abdominal pain upper
         subjects affected / exposed
    10 / 180 (5.56%)
    6 / 178 (3.37%)
         occurrences all number
    11
    6
    Constipation
         subjects affected / exposed
    24 / 180 (13.33%)
    20 / 178 (11.24%)
         occurrences all number
    30
    23
    Diarrhoea
         subjects affected / exposed
    41 / 180 (22.78%)
    31 / 178 (17.42%)
         occurrences all number
    81
    41
    Gastrooesophageal reflux disease
         subjects affected / exposed
    11 / 180 (6.11%)
    7 / 178 (3.93%)
         occurrences all number
    11
    8
    Nausea
         subjects affected / exposed
    29 / 180 (16.11%)
    14 / 178 (7.87%)
         occurrences all number
    36
    18
    Vomiting
         subjects affected / exposed
    21 / 180 (11.67%)
    13 / 178 (7.30%)
         occurrences all number
    27
    13
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    12 / 180 (6.67%)
    6 / 178 (3.37%)
         occurrences all number
    15
    6
    Pruritus
         subjects affected / exposed
    42 / 180 (23.33%)
    32 / 178 (17.98%)
         occurrences all number
    57
    38
    Rash maculo-papular
         subjects affected / exposed
    6 / 180 (3.33%)
    10 / 178 (5.62%)
         occurrences all number
    10
    13
    Rash
         subjects affected / exposed
    9 / 180 (5.00%)
    11 / 178 (6.18%)
         occurrences all number
    10
    13
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    17 / 180 (9.44%)
    22 / 178 (12.36%)
         occurrences all number
    19
    22
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    38 / 180 (21.11%)
    24 / 178 (13.48%)
         occurrences all number
    45
    25
    Back pain
         subjects affected / exposed
    20 / 180 (11.11%)
    25 / 178 (14.04%)
         occurrences all number
    24
    26
    Muscle spasms
         subjects affected / exposed
    11 / 180 (6.11%)
    4 / 178 (2.25%)
         occurrences all number
    12
    6
    Myalgia
         subjects affected / exposed
    11 / 180 (6.11%)
    4 / 178 (2.25%)
         occurrences all number
    12
    4
    Pain in extremity
         subjects affected / exposed
    16 / 180 (8.89%)
    13 / 178 (7.30%)
         occurrences all number
    17
    14
    Musculoskeletal chest pain
         subjects affected / exposed
    5 / 180 (2.78%)
    9 / 178 (5.06%)
         occurrences all number
    6
    10
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    16 / 180 (8.89%)
    11 / 178 (6.18%)
         occurrences all number
    17
    20
    Bronchitis
         subjects affected / exposed
    23 / 180 (12.78%)
    17 / 178 (9.55%)
         occurrences all number
    30
    20
    Rhinitis
         subjects affected / exposed
    10 / 180 (5.56%)
    0 / 178 (0.00%)
         occurrences all number
    12
    0
    Pneumonia
         subjects affected / exposed
    11 / 180 (6.11%)
    9 / 178 (5.06%)
         occurrences all number
    12
    9
    Sinusitis
         subjects affected / exposed
    11 / 180 (6.11%)
    7 / 178 (3.93%)
         occurrences all number
    11
    10
    Upper respiratory tract infection
         subjects affected / exposed
    16 / 180 (8.89%)
    11 / 178 (6.18%)
         occurrences all number
    24
    16
    Urinary tract infection
         subjects affected / exposed
    12 / 180 (6.67%)
    7 / 178 (3.93%)
         occurrences all number
    12
    7
    Metabolism and nutrition disorders
    Hyperkalaemia
         subjects affected / exposed
    15 / 180 (8.33%)
    4 / 178 (2.25%)
         occurrences all number
    20
    4
    Decreased appetite
         subjects affected / exposed
    20 / 180 (11.11%)
    16 / 178 (8.99%)
         occurrences all number
    22
    20
    Hypomagnesaemia
         subjects affected / exposed
    10 / 180 (5.56%)
    4 / 178 (2.25%)
         occurrences all number
    18
    5
    Hypokalaemia
         subjects affected / exposed
    10 / 180 (5.56%)
    8 / 178 (4.49%)
         occurrences all number
    16
    10
    Hypophosphataemia
         subjects affected / exposed
    12 / 180 (6.67%)
    3 / 178 (1.69%)
         occurrences all number
    17
    3

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Dec 2015
     Allows enrollment of subjects who are ineligible for or refuse chemotherapy in the first-line advanced non-small cell lung cancer setting  Allows use of flat dose in the pre-study period and during the investigational period.  Added HIV testing as a screening test
    12 Feb 2016
    Change the Human Immunodeficiency Virus criterion to reflect the language that is used across the nivolumab clinical development program and adjusted the frequency of magnetic resonance imaging scans in those with a history of brain metastasis to align with study assessments.
    12 Aug 2016
     To change the pre-study nivolumab requirement  Add a small increase to the sample size  Add immunogenicity as an endpoint  Make small changes to the laboratory and tumor assessments and duration of contraception use to align the protocol with updates to the nivolumab clinical development program.
    09 Feb 2018
     Included additional language for nivolumab program level updates  Added information for interim analysis
    18 Jun 2018
     Reduced sample size and modified primary endpoint from noninferiority to one-sided confidence interval around the differences of PFS rates  Modified follow-up for overall survival for 3 years  Added rationale for maximum treatment duration with nivolumab of 2 years

    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.
    No formal statistical analyses were conducted. Median OS was not reached in either arm.
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    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.

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