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    Clinical Trial Results:
    Phase 1/2 Study to Evaluate the Safety and Preliminary Efficacy of Nivolumab Combined with Daratumumab in Participants with Advanced or Metastatic Solid Tumors

    Summary
    EudraCT number
    2017-000367-33
    Trial protocol
    DE   ES   FR   IT  
    Global end of trial date
    02 Jul 2020

    Results information
    Results version number
    v1(current)
    This version publication date
    18 Jul 2021
    First version publication date
    18 Jul 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CA209-9GW
    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
    15 Apr 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    02 Jul 2020
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Jul 2020
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To establish the tolerability of the combination of Nivolumab and Daratumumab in participants with advanced or metastatic solid tumors.
    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
    15 Jun 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 1
    Country: Number of subjects enrolled
    United States: 28
    Country: Number of subjects enrolled
    France: 32
    Country: Number of subjects enrolled
    Germany: 3
    Country: Number of subjects enrolled
    Italy: 10
    Country: Number of subjects enrolled
    Spain: 19
    Country: Number of subjects enrolled
    Switzerland: 12
    Worldwide total number of subjects
    105
    EEA total number of subjects
    64
    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)
    74
    From 65 to 84 years
    31
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    105 participants treated

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Nivolumab + Daratumumab (TNBC)
    Arm description
    Triple-negative breast cancer (TNBC) treated with Triple-negative breast cancer (TNBC) treated with Nivolumab IV 240 mg Q2W (weeks 3 to 24) + Daratumumab IV 16 mg/kg Q1W (weeks 1 to 8), Daratumumab IV 16 mg/kg Q2W (weeks 9-24)
    Arm type
    Experimental

    Investigational medicinal product name
    Nivolumab+Daratumumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Nivolumab IV 240 mg Q2W (weeks 3 to 24) + Daratumumab IV 16 mg/kg Q1W (weeks 1 to 8), Daratumumab IV 16 mg/kg Q2W (weeks 9-24)

    Arm title
    Nivolumab + Daratumumab (NSCLC)
    Arm description
    Non-small cell lung cancer (NSCLC) treated with Nivolumab IV 240 mg Q2W (weeks 3 to 24) + Daratumumab IV 16 mg/kg Q1W (weeks 1 to 8), Daratumumab IV 16 mg/kg Q2W (weeks 9-24)
    Arm type
    Experimental

    Investigational medicinal product name
    Nivolumab+Daratumumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Nivolumab IV 240 mg Q2W (weeks 3 to 24) + Daratumumab IV 16 mg/kg Q1W (weeks 1 to 8), Daratumumab IV 16 mg/kg Q2W (weeks 9-24)

    Arm title
    Nivolumab + Daratumumab (PAC)
    Arm description
    Pancreatic adenocarcinoma cancer (PAC) treated with Nivolumab IV 240 mg Q2W (weeks 3 to 24) + Daratumumab IV 16 mg/kg Q1W (weeks 1 to 8), Daratumumab IV 16 mg/kg Q2W (weeks 9-24)
    Arm type
    Experimental

    Investigational medicinal product name
    Nivolumab+Daratumumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Nivolumab IV 240 mg Q2W (weeks 3 to 24) + Daratumumab IV 16 mg/kg Q1W (weeks 1 to 8), Daratumumab IV 16 mg/kg Q2W (weeks 9-24)

    Number of subjects in period 1
    Nivolumab + Daratumumab (TNBC) Nivolumab + Daratumumab (NSCLC) Nivolumab + Daratumumab (PAC)
    Started
    41
    21
    43
    Completed
    0
    1
    0
    Not completed
    41
    20
    43
         Study Drug Toxicity
    2
    1
    -
         Disease Progression
    30
    19
    41
         Adverse event, serious fatal
    1
    -
    -
         Administrative reason by sponsor
    -
    -
    1
         Other reasons
    2
    -
    -
         Adverse Event unrelated to Study Drug
    6
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Nivolumab + Daratumumab (TNBC)
    Reporting group description
    Triple-negative breast cancer (TNBC) treated with Triple-negative breast cancer (TNBC) treated with Nivolumab IV 240 mg Q2W (weeks 3 to 24) + Daratumumab IV 16 mg/kg Q1W (weeks 1 to 8), Daratumumab IV 16 mg/kg Q2W (weeks 9-24)

    Reporting group title
    Nivolumab + Daratumumab (NSCLC)
    Reporting group description
    Non-small cell lung cancer (NSCLC) treated with Nivolumab IV 240 mg Q2W (weeks 3 to 24) + Daratumumab IV 16 mg/kg Q1W (weeks 1 to 8), Daratumumab IV 16 mg/kg Q2W (weeks 9-24)

    Reporting group title
    Nivolumab + Daratumumab (PAC)
    Reporting group description
    Pancreatic adenocarcinoma cancer (PAC) treated with Nivolumab IV 240 mg Q2W (weeks 3 to 24) + Daratumumab IV 16 mg/kg Q1W (weeks 1 to 8), Daratumumab IV 16 mg/kg Q2W (weeks 9-24)

    Reporting group values
    Nivolumab + Daratumumab (TNBC) Nivolumab + Daratumumab (NSCLC) Nivolumab + Daratumumab (PAC) Total
    Number of subjects
    41 21 43 105
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0
        Newborns (0-27 days)
    0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0
        Children (2-11 years)
    0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0
        Adults (18-64 years)
    31 17 26 74
        From 65-84 years
    10 4 17 31
        85 years and over
    0 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    55.1 ± 13.1 59.5 ± 8.5 61.9 ± 9.4 -
    Sex: Female, Male
    Units: Participants
        Female
    41 7 20 68
        Male
    0 14 23 37
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 0 0 0
        Asian
    2 0 0 2
        Native Hawaiian or Other Pacific Islander
    0 0 0 0
        Black or African American
    1 0 0 1
        White
    33 21 35 89
        More than one race
    0 0 0 0
        Other
    5 0 8 13
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    1 0 0 1
        Not Hispanic or Latino
    20 3 21 44
        Unknown or Not Reported
    20 18 22 60

    End points

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    End points reporting groups
    Reporting group title
    Nivolumab + Daratumumab (TNBC)
    Reporting group description
    Triple-negative breast cancer (TNBC) treated with Triple-negative breast cancer (TNBC) treated with Nivolumab IV 240 mg Q2W (weeks 3 to 24) + Daratumumab IV 16 mg/kg Q1W (weeks 1 to 8), Daratumumab IV 16 mg/kg Q2W (weeks 9-24)

    Reporting group title
    Nivolumab + Daratumumab (NSCLC)
    Reporting group description
    Non-small cell lung cancer (NSCLC) treated with Nivolumab IV 240 mg Q2W (weeks 3 to 24) + Daratumumab IV 16 mg/kg Q1W (weeks 1 to 8), Daratumumab IV 16 mg/kg Q2W (weeks 9-24)

    Reporting group title
    Nivolumab + Daratumumab (PAC)
    Reporting group description
    Pancreatic adenocarcinoma cancer (PAC) treated with Nivolumab IV 240 mg Q2W (weeks 3 to 24) + Daratumumab IV 16 mg/kg Q1W (weeks 1 to 8), Daratumumab IV 16 mg/kg Q2W (weeks 9-24)

    Primary: Number of Participants with Adverse Events (AEs)

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    End point title
    Number of Participants with Adverse Events (AEs) [1]
    End point description
    Number of participants with any grade of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine the safety and tolerability of Nivolumab and Daratumumab
    End point type
    Primary
    End point timeframe
    From first dose to 30 days post last dose (up to 34 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 + Daratumumab (TNBC) Nivolumab + Daratumumab (NSCLC) Nivolumab + Daratumumab (PAC)
    Number of subjects analysed
    41
    21
    43
    Units: Participants
    41
    21
    42
    No statistical analyses for this end point

    Primary: Number of Participants with Serious Adverse Events (SAEs)

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    End point title
    Number of Participants with Serious Adverse Events (SAEs) [2]
    End point description
    Number of participants with any grade of serious adverse events (SAEs) graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine the safety and tolerability of Nivolumab and Daratumumab
    End point type
    Primary
    End point timeframe
    From first dose to 30 days post last dose (up to 34 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: Only summary statistics planned for this endpoint
    End point values
    Nivolumab + Daratumumab (TNBC) Nivolumab + Daratumumab (NSCLC) Nivolumab + Daratumumab (PAC)
    Number of subjects analysed
    41
    21
    43
    Units: Participants
    29
    14
    29
    No statistical analyses for this end point

    Primary: Number of Participants with Laboratory Abnormalities in Specific Liver Tests

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    End point title
    Number of Participants with Laboratory Abnormalities in Specific Liver Tests [3]
    End point description
    Number of participants with laboratory abnormalities in specific liver tests based on US conventional units to determine the safety and tolerability of Nivolumab and Daratumumab. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized: - ALT or AST > 3 x ULN, > 5 x ULN, > 10 x ULN and > 20 x ULN - Total bilirubin > 2 x ULN - ALP > 1.5 x ULN - Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 1.5 x ULN - Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 1.5 x ULN - Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN - Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN
    End point type
    Primary
    End point timeframe
    From first dose to 30 days post last dose (up to 34 months)
    Notes
    [3] - 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 + Daratumumab (TNBC) Nivolumab + Daratumumab (NSCLC) Nivolumab + Daratumumab (PAC)
    Number of subjects analysed
    37
    21
    43
    Units: Participants
        ALT OR AST > 3XULN
    6
    2
    10
        ALT OR AST > 5XULN
    5
    2
    6
        ALT OR AST > 10XULN
    2
    1
    3
        ALT OR AST > 20XULN
    0
    0
    0
        TOTAL BILIRUBIN > 2XULN
    1
    1
    8
        ALP > 1.5XULN
    10
    5
    34
        ALT/AST ELEV>3XULN WITH TTL BILI>1.5XULN w/ 1 DAY
    1
    1
    5
        ALT/AST ELEV>3XULN w/ TTL BILI>1.5XULN w/ 30 DAYS
    1
    1
    5
        ALT/AST ELEV>3XULN WITH TOTAL BILI>2XULN w/ 1 DAY
    1
    1
    5
        ALT/AST ELEV>3XULN w/ TOTAL BILI>2XULN w/ 30 DAYS
    1
    1
    5
    No statistical analyses for this end point

    Primary: Number of Participants with Laboratory Abnormalities in Specific Thyroid Tests

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    End point title
    Number of Participants with Laboratory Abnormalities in Specific Thyroid Tests [4]
    End point description
    Number of participants with laboratory abnormalities in specific thyroid tests based on US conventional units to determine the safety and tolerability of Nivolumab and Daratumumab. The number of subjects with the following laboratory abnormalities from on-treatment evaluations will be summarized: - TSH value > ULN and - with baseline TSH value <= ULN - with at least one FT3/FT4 test value < LLN within 2-week window after the abnormal TSH test - with all FT3/FT4 test values >= LLN within 2-week window after the abnormal TSH test - with FT3/FT4 missing within 2-week window after the abnormal TSH test. - TSH < LLN and - with baseline TSH value >= LLN - with at least one FT3/FT4 test value > ULN within 2-week window after the abnormal TSH test - with all FT3/FT4 test values <= ULN within 2-week window after the abnormal TSH test - with FT3/FT4 missing within 2-week window after the abnormal TSH test
    End point type
    Primary
    End point timeframe
    From first dose to 30 days post last dose (up to 34 months)
    Notes
    [4] - 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 + Daratumumab (TNBC) Nivolumab + Daratumumab (NSCLC) Nivolumab + Daratumumab (PAC)
    Number of subjects analysed
    16
    15
    21
    Units: Participants
        TSH > ULN
    4
    3
    4
        TSH>ULN w/ TSH<=ULN AT BASELINE
    4
    3
    2
        TSH>ULN w/ AT LEAST ONE FT3/FT4 TEST VALUE<LLN
    1
    1
    3
        TSH>ULN w/ ALL OTHER FT3/FT4 TEST VALUES>=LLN
    2
    2
    0
        TSH>ULN w/ FT3/FT4 TEST MISSING
    1
    0
    1
        TSH < LLN
    1
    2
    2
        TSH<LLN w/ TSH>=LLN AT BASELINE
    1
    2
    1
        TSH<LLN w/ AT LEAST ONE FT3/FT4 TEST VALUE>ULN
    1
    0
    0
        TSH<LLN w/ ALL OTHER FT3/FT4 TEST VALUES<=ULN
    0
    2
    1
        TSH<LLN w/ FT3/FT4 TEST MISSING
    0
    0
    1
    No statistical analyses for this end point

    Primary: Number of Participants with Laboratory Results of Worst CTC Grade

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    End point title
    Number of Participants with Laboratory Results of Worst CTC Grade [5]
    End point description
    Number of participants with laboratory test results of worst (CTC v4.0) grades 0-4 to determine the safety and tolerability of Nivolumab and Daratumumab
    End point type
    Primary
    End point timeframe
    From first dose to 30 days post last dose (up to 34 months)
    Notes
    [5] - 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 + Daratumumab (TNBC) Nivolumab + Daratumumab (NSCLC) Nivolumab + Daratumumab (PAC)
    Number of subjects analysed
    41
    21
    43
    Units: Participants
        Hemoglobin Grade 0
    13
    5
    5
        Hemoglobin Grade 1
    14
    9
    23
        Hemoglobin Grade 2
    7
    7
    12
        Hemoglobin Grade 3
    5
    0
    3
        Hemoglobin Not Reported
    2
    0
    0
        Platelet Count Grade 0
    29
    16
    24
        Platelet Count Grade 1
    4
    4
    18
        Platelet Count Grade 2
    0
    0
    0
        Platelet Count Grade 3
    1
    1
    1
        Platelet Count Grade 4
    5
    0
    0
        Platelet Count Not Reported
    2
    0
    0
        Leukocytes Grade 0
    27
    18
    35
        Leukocytes Grade 1
    7
    1
    3
        Leukocytes Grade 2
    4
    1
    5
        Leukocytes Grade 3
    1
    1
    0
        Leukocytes Grade 4
    0
    0
    0
        Leukocytes Not Reported
    2
    0
    0
        Alkaline Phosphatase Grade 0
    23
    13
    6
        Alkaline Phosphatase Grade 1
    7
    4
    11
        Alkaline Phosphatase Grade 2
    4
    1
    13
        Alkaline Phosphatase Grade 3
    2
    3
    13
        Alkaline Phosphatase Grade 4
    0
    0
    0
        Alkaline Phosphatase Not Reported
    5
    0
    0
        Aspartate Aminotransferase Grade 0
    16
    16
    20
        Aspartate Aminotransferase Grade 1
    15
    3
    13
        Aspartate Aminotransferase Grade 2
    2
    1
    5
        Aspartate Aminotransferase Grade 3
    4
    1
    5
        Aspartate Aminotransferase Grade 4
    0
    0
    0
        Aspartate Aminotransferase Not Reported
    4
    0
    0
        Alanine Aminotransferase Grade 0
    19
    12
    19
        Alanine Aminotransferase Grade 1
    15
    6
    19
        Alanine Aminotransferase Grade 2
    1
    0
    1
        Alanine Aminotransferase Grade 3
    2
    2
    4
        Alanine Aminotransferase Grade 4
    0
    0
    0
        Alanine Aminotransferase Not Reported
    4
    1
    0
        Bilirubin Grade 0
    30
    18
    30
        Bilirubin Grade 1
    5
    1
    4
        Bilirubin Grade 2
    0
    1
    3
        Bilirubin Grade 3
    1
    1
    6
        Bilirubin Grade 4
    0
    0
    0
        Bilirubin Not Reported
    5
    0
    0
        Creatinine Grade 0
    30
    15
    38
        Creatinine Grade 1
    5
    5
    4
        Creatinine Grade 2
    1
    1
    0
        Creatinine Grade 3
    0
    0
    0
        Creatinine Grade 4
    0
    0
    0
        Creatinine Not Reported
    5
    0
    1
        Phosphorous Grade 0
    29
    15
    33
        Phosphorous Grade 1
    0
    0
    2
        Phosphorous Grade 2
    4
    5
    4
        Phosphorous Grade 3
    2
    1
    3
        Phosphorous Grade 4
    0
    0
    0
        Phosphorous Not Reported
    6
    0
    1
        Albumin Grade 0
    15
    15
    15
        Albumin Grade 1
    13
    4
    14
        Albumin Grade 2
    6
    2
    12
        Albumin Grade 3
    0
    0
    1
        Albumin Grade 4
    0
    0
    0
        Albumin Not Reported
    7
    0
    1
        Amylase Grade 0
    9
    5
    36
        Amylase Grade 1
    1
    2
    1
        Amylase Grade 2
    0
    1
    0
        Amylase Grade 3
    0
    0
    1
        Amylase Grade 4
    0
    0
    0
        Amylase Not Reported
    31
    13
    5
        Lipase Grade 0
    15
    6
    31
        Lipase Grade 1
    1
    1
    5
        Lipase Grade 2
    0
    1
    1
        Lipase Grade 3
    0
    0
    3
        Lipase Grade 4
    0
    0
    1
        Lipase Not Reported
    25
    13
    2
        Hypernatremia Grade 0
    35
    20
    42
        Hypernatremia Grade 1
    1
    0
    0
        Hypernatremia Grade 2
    0
    0
    0
        Hypernatremia Grade 3
    0
    0
    0
        Hypernatremia Grade 4
    0
    0
    0
        Hypernatremia Not Reported
    5
    1
    1
        Hyponatremia Grade 0
    23
    12
    20
        Hyponatremia Grade 1
    12
    7
    15
        Hyponatremia Grade 2
    0
    0
    0
        Hyponatremia Grade 3
    1
    1
    7
        Hyponatremia Grade 4
    0
    0
    0
        Hyponatremia Not Reported
    5
    1
    1
        Hyperkalemia Grade 0
    30
    17
    35
        Hyperkalemia Grade 1
    4
    3
    5
        Hyperkalemia Grade 2
    3
    0
    1
        Hyperkalemia Grade 3
    0
    0
    1
        Hyperkalemia Grade 4
    0
    0
    0
        Hyperkalemia Not Reported
    4
    1
    1
        Hypokalemia Grade 0
    33
    19
    33
        Hypokalemia Grade 1
    4
    1
    6
        Hypokalemia Grade 2
    0
    0
    0
        Hypokalemia Grade 3
    0
    0
    3
        Hypokalemia Grade 4
    0
    0
    0
        Hypokalemia Not Reported
    4
    1
    1
        Hypercalcemia Grade 0
    33
    16
    42
        Hypercalcemia Grade 1
    2
    4
    0
        Hypercalcemia Grade 2
    0
    1
    0
        Hypercalcemia Grade 3
    0
    0
    0
        Hypercalcemia Grade 4
    0
    0
    0
        Hypercalcemia Not Reported
    6
    0
    1
        Hypocalcemia Grade 0
    25
    14
    15
        Hypocalcemia Grade 1
    8
    7
    21
        Hypocalcemia Grade 2
    2
    0
    6
        Hypocalcemia Grade 3
    0
    0
    0
        Hypocalcemia Grade 4
    0
    0
    0
        Hypocalcemia Not Reported
    6
    0
    1
        Hypermagnesemia Grade 0
    34
    21
    40
        Hypermagnesemia Grade 1
    1
    0
    2
        Hypermagnesemia Grade 2
    0
    0
    0
        Hypermagnesemia Grade 3
    0
    0
    0
        Hypermagnesemia Grade 4
    0
    0
    0
        Hypermagnesemia Not Reported
    6
    0
    1
        Hypomagnesemia Grade 0
    33
    17
    38
        Hypomagnesemia Grade 1
    2
    4
    4
        Hypomagnesemia Grade 2
    0
    0
    0
        Hypomagnesemia Grade 3
    0
    0
    0
        Hypomagnesemia Grade 4
    0
    0
    0
        Hypomagnesemia Not Reported
    6
    0
    1
        Hyperglycemia Grade 0
    10
    1
    7
        Hyperglycemia Grade 1
    9
    4
    6
        Hyperglycemia Grade 2
    0
    1
    1
        Hyperglycemia Grade 3
    0
    0
    1
        Hyperglycemia Grade 4
    0
    0
    0
        Hyperglycemia Not Reported
    22
    15
    28
        Hypoglycemia Grade 0
    19
    6
    14
        Hypoglycemia Grade 1
    0
    0
    1
        Hypoglycemia Grade 2
    0
    0
    1
        Hypoglycemia Grade 3
    0
    0
    0
        Hypoglycemia Grade 4
    0
    0
    0
        Hypoglycemia Not Reported
    22
    15
    27
    No statistical analyses for this end point

    Secondary: Objective Response Rate (ORR)

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    End point title
    Objective Response Rate (ORR)
    End point description
    Objective response rate (ORR) is defined as the percentage of treated participants who achieve a best response of complete response (CR) or partial response (PR) based on investigator assessments (using RECIST v1.1 criteria)
    End point type
    Secondary
    End point timeframe
    Up to 36 months
    End point values
    Nivolumab + Daratumumab (TNBC) Nivolumab + Daratumumab (NSCLC) Nivolumab + Daratumumab (PAC)
    Number of subjects analysed
    41
    21
    43
    Units: Percentage of Participants
        number (confidence interval 95%)
    4.9 (0.6 to 16.5)
    9.5 (1.2 to 30.4)
    0 (0.0 to 8.2)
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR)

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    End point title
    Duration of Response (DOR)
    End point description
    Duration of response (DOR) is defined as the time between the date of first documented response (Complete response or partial response) to the date of the first documented tumor progression as determined by Investigator (per RECIST v1.1 criteria), or death due to any cause, whichever occurs first
    End point type
    Secondary
    End point timeframe
    Up to 36 months
    End point values
    Nivolumab + Daratumumab (TNBC) Nivolumab + Daratumumab (NSCLC) Nivolumab + Daratumumab (PAC)
    Number of subjects analysed
    2
    2
    0 [6]
    Units: Months
        median (confidence interval 95%)
    4.17 (00000 to 99999)
    9.40 (7.72 to 11.07)
    ( to )
    Notes
    [6] - There were no patients with BOR in this arm.
    No statistical analyses for this end point

    Secondary: Best Overall Response (BOR)

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    End point title
    Best Overall Response (BOR)
    End point description
    Best overall response (BOR) is defined as the best response, as determined by Investigator, recorded between the date of first dose and the date of objectively documented progression per RECIST v1.1 criteria or the date of subsequent therapy, whichever occurs first.
    End point type
    Secondary
    End point timeframe
    Up to 36 months
    End point values
    Nivolumab + Daratumumab (TNBC) Nivolumab + Daratumumab (NSCLC) Nivolumab + Daratumumab (PAC)
    Number of subjects analysed
    41
    21
    43
    Units: Participants
        Complete Response (CR)
    0
    0
    0
        Partial Response (PR)
    2
    2
    0
        Stable Disease (SD)
    8
    10
    9
        Progressive Disease (PD)
    22
    9
    31
        Unable to Determine (UTD)
    9
    0
    3
    No statistical analyses for this end point

    Secondary: Progression Free Survival (PFS)

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    End point title
    Progression Free Survival (PFS)
    End point description
    Progression Free Survival (PFS) is defined as the time between the date of treatment start day and the date of first documented tumor progression, based on Investigator assessments (per RECIST v1.1 criteria), or death due to any cause, whichever occurs first.
    End point type
    Secondary
    End point timeframe
    Up to 36 months
    End point values
    Nivolumab + Daratumumab (TNBC) Nivolumab + Daratumumab (NSCLC) Nivolumab + Daratumumab (PAC)
    Number of subjects analysed
    41
    21
    43
    Units: Months
        median (confidence interval 95%)
    1.22 (1.15 to 1.41)
    4.85 (1.12 to 7.69)
    1.22 (1.15 to 1.38)
    No statistical analyses for this end point

    Secondary: Nivolumab Serum Concentrations

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    End point title
    Nivolumab Serum Concentrations
    End point description
    Pharmacokinetics (PK) assessed using serum concentration data for Nivolumab
    End point type
    Secondary
    End point timeframe
    From day 1 to follow-up 2 (up to 36 months)
    End point values
    Nivolumab + Daratumumab (TNBC) Nivolumab + Daratumumab (NSCLC) Nivolumab + Daratumumab (PAC)
    Number of subjects analysed
    12 [7]
    11 [8]
    16 [9]
    Units: µg/mL
    geometric mean (geometric coefficient of variation)
        Cycle 3 Day 1
    52.9 ± 34.8
    43.5 ± 26.6
    42.5 ± 29.7
        Cycle 4 Day 1
    87.0 ± 34.0
    77.9 ± 37.6
    64.3 ± 31.4
        Cycle 7 Day 1
    44.8 ± 32.8
    116.2 ± 23.8
    83.3 ± 99999
        Cycle 11 Day 1
    99999 ± 99999
    124.3 ± 46.5
    99999 ± 99999
        Follow-up 1
    48.9 ± 44.0
    71.6 ± 58.9
    32.8 ± 48.6
        Follow-up 2
    23.5 ± 60.6
    17.4 ± 96.1
    6.3 ± 89.7
    Notes
    [7] - cycle 3=12 subjects cycle 4=6 subjects cycle 7=2 subjects FU1=7 subjects FU2=5 subjects
    [8] - cycle3=11subjects cycle4=11subjects cycle7=8subjects cycle11=4subjects FU1=7subjects FU2=3subjects
    [9] - cycle 3=16 subjects cycle 4=5 subjects cycle 7=1 subjects FU1=9 subjects FU2=4 subjects
    No statistical analyses for this end point

    Secondary: Daratumumab Serum Concentrations

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    End point title
    Daratumumab Serum Concentrations
    End point description
    Pharmacokinetics (PK) assessed using serum concentration data for Daratumumab
    End point type
    Secondary
    End point timeframe
    From day 1 to follow-up 2 (up to 36 months)
    End point values
    Nivolumab + Daratumumab (TNBC) Nivolumab + Daratumumab (NSCLC) Nivolumab + Daratumumab (PAC)
    Number of subjects analysed
    31 [10]
    21 [11]
    38 [12]
    Units: µg/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1 (hour 8)
    334.1819 ± 28.1
    310.7272 ± 15.6
    277.6708 ± 28.4
        Cycle 2 Day 1 (hour 0)
    332.9353 ± 29.6
    321.6084 ± 25.7
    275.1521 ± 35.9
        Cycle 2 Day 1 (hour 4)
    735.2131 ± 36.9
    641.8146 ± 26.3
    569.8158 ± 27.4
        Cycle 3 day 1
    629.9607 ± 19.8
    477.6488 ± 25.0
    473.0335 ± 23.8
        Cycle 4 day 1
    559.8988 ± 31.0
    393.5442 ± 48.9
    406.9487 ± 28.2
        Cycle 7 day 1
    294.8322 ± 99999
    515.2495 ± 21.9
    229.0854 ± 99999
        Follow-up 1
    177.5615 ± 65.0
    157.5960 ± 62.2
    184.1510 ± 51.7
        Follow-up 2
    134.0478 ± 99999
    57.3349 ± 99999
    8.4517 ± 158.4
    Notes
    [10] - Subjects analyzed: C1=31 C2(0)=25 C2(4)=24 C3=10 C4=5 C7=1 FU1=6 FU2=1
    [11] - Subjects analyzed: C1=21 C2(0)=12 C2(4)=11 C3=10 C4=7 C7=4 FU1=5 FU2=1
    [12] - Subjects analyzed: C1=38 C2(0)=28 C2(4)=28 C3=13 C4=5 C7=1 FU1=9 FU2=4
    No statistical analyses for this end point

    Secondary: Percentage of Participants Anti Drug Antibody (ADA) by Positivity

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    End point title
    Percentage of Participants Anti Drug Antibody (ADA) by Positivity
    End point description
    Percentage of participants Anti Drug Antibody (ADA) to assess immunogenicity by ADA positive status and ADA negative status, relative to baseline. ADA positive is a participant with at least one ADA-positive sample relative to baseline (ADA negative at baseline or ADA titer to be at least 4-fold or greater (>=) than baseline positive titer) at any time after initiation of treatment. ADA Negative is a participant with no ADA-positive sample after initiation of treatment
    End point type
    Secondary
    End point timeframe
    Up to 36 months
    End point values
    Nivolumab + Daratumumab (TNBC) Nivolumab + Daratumumab (NSCLC) Nivolumab + Daratumumab (PAC)
    Number of subjects analysed
    41 [13]
    21 [14]
    43 [15]
    Units: Percentage of Participants
    number (not applicable)
        Nivolumab Baseline ADA positive
    0.00
    6.3
    0.00
        Daratumumab Baseline ADA positive
    0.00
    5.6
    0.00
        Nivolumab ADA Positive
    0.00
    0.00
    0.00
        Nivolumab ADA Negative
    100.0
    100.0
    100.0
        Daratumumab ADA Positive
    0.00
    0.00
    0.00
        Daratumumab ADA Negative
    100.0
    100.0
    100.0
    Notes
    [13] - Nivolumab =17 subjects analyzed Daratumumab = 29 subjects analyzed
    [14] - Nivolumab = 16 subjects analyzed Daratumumab = 18 subjects analyzed
    [15] - Nivolumab = 18 subjects analyzed Daratumumab = 33 subjects analyzed
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All adverse events were collected from the first dose up to 100 days after the last treatment dose
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Nivolumab + Daratumumab (TNBC)
    Reporting group description
    Triple-negative breast cancer (TNBC) treated with Triple-negative breast cancer (TNBC) treated with Nivolumab IV 240 mg Q2W (weeks 3 to 24) + Daratumumab IV 16 mg/kg Q1W (weeks 1 to 8), Daratumumab IV 16 mg/kg Q2W (weeks 9-24)

    Reporting group title
    Nivolumab + Daratumumab (PAC)
    Reporting group description
    Pancreatic adenocarcinoma cancer (PAC) treated with Nivolumab IV 240 mg Q2W (weeks 3 to 24) + Daratumumab IV 16 mg/kg Q1W (weeks 1 to 8), Daratumumab IV 16 mg/kg Q2W (weeks 9-24)

    Reporting group title
    Nivolumab + Daratumumab (NSCLC)
    Reporting group description
    Non-small cell lung cancer (NSCLC) treated with Nivolumab IV 240 mg Q2W (weeks 3 to 24) + Daratumumab IV 16 mg/kg Q1W (weeks 1 to 8), Daratumumab IV 16 mg/kg Q2W (weeks 9-24)

    Serious adverse events
    Nivolumab + Daratumumab (TNBC) Nivolumab + Daratumumab (PAC) Nivolumab + Daratumumab (NSCLC)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    36 / 41 (87.80%)
    36 / 43 (83.72%)
    17 / 21 (80.95%)
         number of deaths (all causes)
    29
    36
    11
         number of deaths resulting from adverse events
    Vascular disorders
    Embolism
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    22 / 41 (53.66%)
    26 / 43 (60.47%)
    8 / 21 (38.10%)
         occurrences causally related to treatment / all
    0 / 23
    0 / 30
    0 / 12
         deaths causally related to treatment / all
    0 / 18
    0 / 29
    0 / 6
    Metastases to central nervous system
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastases to spinal cord
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour pain
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Tumour thrombosis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    2 / 41 (4.88%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Generalised oedema
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    2 / 41 (4.88%)
    4 / 43 (9.30%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Disorientation
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fracture
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    C-reactive protein increased
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General physical condition abnormal
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Liver function test abnormal
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Procalcitonin increased
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile bone marrow aplasia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 41 (2.44%)
    2 / 43 (4.65%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Dyspnoea exertional
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    8 / 41 (19.51%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    2 / 41 (4.88%)
    2 / 43 (4.65%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic encephalopathy
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 41 (0.00%)
    3 / 43 (6.98%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 41 (0.00%)
    2 / 43 (4.65%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Hepatobiliary disorders
    Cholestasis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Haematuria
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary incontinence
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash papular
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Flank pain
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Lung abscess
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nosocomial infection
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritonitis bacterial
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    2 / 21 (9.52%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    2 / 21 (9.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Nivolumab + Daratumumab (TNBC) Nivolumab + Daratumumab (PAC) Nivolumab + Daratumumab (NSCLC)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    40 / 41 (97.56%)
    42 / 43 (97.67%)
    21 / 21 (100.00%)
    Vascular disorders
    Flushing
         subjects affected / exposed
    3 / 41 (7.32%)
    2 / 43 (4.65%)
    2 / 21 (9.52%)
         occurrences all number
    6
    2
    2
    Hypotension
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    2
    Lymphoedema
         subjects affected / exposed
    3 / 41 (7.32%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    3
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant neoplasm progression
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    2
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    6 / 41 (14.63%)
    7 / 43 (16.28%)
    5 / 21 (23.81%)
         occurrences all number
    9
    7
    5
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    12 / 41 (29.27%)
    11 / 43 (25.58%)
    12 / 21 (57.14%)
         occurrences all number
    24
    21
    16
    Chest pain
         subjects affected / exposed
    9 / 41 (21.95%)
    1 / 43 (2.33%)
    1 / 21 (4.76%)
         occurrences all number
    14
    1
    1
    Chills
         subjects affected / exposed
    3 / 41 (7.32%)
    4 / 43 (9.30%)
    2 / 21 (9.52%)
         occurrences all number
    3
    7
    2
    Fatigue
         subjects affected / exposed
    8 / 41 (19.51%)
    15 / 43 (34.88%)
    3 / 21 (14.29%)
         occurrences all number
    25
    23
    10
    Mucosal inflammation
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 43 (0.00%)
    3 / 21 (14.29%)
         occurrences all number
    2
    0
    3
    Non-cardiac chest pain
         subjects affected / exposed
    3 / 41 (7.32%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    6
    0
    1
    Oedema peripheral
         subjects affected / exposed
    5 / 41 (12.20%)
    10 / 43 (23.26%)
    7 / 21 (33.33%)
         occurrences all number
    5
    13
    11
    Pain
         subjects affected / exposed
    4 / 41 (9.76%)
    1 / 43 (2.33%)
    5 / 21 (23.81%)
         occurrences all number
    4
    1
    6
    Pyrexia
         subjects affected / exposed
    10 / 41 (24.39%)
    14 / 43 (32.56%)
    7 / 21 (33.33%)
         occurrences all number
    20
    27
    18
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    8 / 41 (19.51%)
    4 / 43 (9.30%)
    2 / 21 (9.52%)
         occurrences all number
    8
    4
    2
    Insomnia
         subjects affected / exposed
    1 / 41 (2.44%)
    3 / 43 (6.98%)
    1 / 21 (4.76%)
         occurrences all number
    1
    4
    1
    Depression
         subjects affected / exposed
    3 / 41 (7.32%)
    2 / 43 (4.65%)
    0 / 21 (0.00%)
         occurrences all number
    4
    2
    0
    Sleep disorder
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    5 / 21 (23.81%)
         occurrences all number
    1
    0
    7
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    18 / 41 (43.90%)
    18 / 43 (41.86%)
    11 / 21 (52.38%)
         occurrences all number
    28
    28
    14
    Fall
         subjects affected / exposed
    0 / 41 (0.00%)
    3 / 43 (6.98%)
    0 / 21 (0.00%)
         occurrences all number
    0
    3
    0
    Vascular access site pain
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    2
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    5 / 41 (12.20%)
    3 / 43 (6.98%)
    0 / 21 (0.00%)
         occurrences all number
    8
    4
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    6 / 41 (14.63%)
    4 / 43 (9.30%)
    0 / 21 (0.00%)
         occurrences all number
    9
    5
    0
    Blood albumin decreased
         subjects affected / exposed
    3 / 41 (7.32%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    3
    0
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    3 / 41 (7.32%)
    6 / 43 (13.95%)
    2 / 21 (9.52%)
         occurrences all number
    4
    9
    2
    Blood bilirubin increased
         subjects affected / exposed
    2 / 41 (4.88%)
    4 / 43 (9.30%)
    0 / 21 (0.00%)
         occurrences all number
    3
    4
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    3 / 41 (7.32%)
    1 / 43 (2.33%)
    0 / 21 (0.00%)
         occurrences all number
    3
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    3 / 41 (7.32%)
    4 / 43 (9.30%)
    0 / 21 (0.00%)
         occurrences all number
    4
    6
    0
    Lymphocyte count decreased
         subjects affected / exposed
    1 / 41 (2.44%)
    3 / 43 (6.98%)
    2 / 21 (9.52%)
         occurrences all number
    2
    5
    7
    Platelet count decreased
         subjects affected / exposed
    3 / 41 (7.32%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    5
    0
    0
    Transaminases increased
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    2
    Weight decreased
         subjects affected / exposed
    1 / 41 (2.44%)
    6 / 43 (13.95%)
    3 / 21 (14.29%)
         occurrences all number
    1
    10
    11
    White blood cell count decreased
         subjects affected / exposed
    1 / 41 (2.44%)
    3 / 43 (6.98%)
    0 / 21 (0.00%)
         occurrences all number
    1
    3
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    8 / 41 (19.51%)
    7 / 43 (16.28%)
    6 / 21 (28.57%)
         occurrences all number
    17
    10
    10
    Lymphopenia
         subjects affected / exposed
    2 / 41 (4.88%)
    1 / 43 (2.33%)
    3 / 21 (14.29%)
         occurrences all number
    2
    1
    5
    Thrombocytopenia
         subjects affected / exposed
    5 / 41 (12.20%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    17
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    15 / 41 (36.59%)
    10 / 43 (23.26%)
    6 / 21 (28.57%)
         occurrences all number
    32
    12
    9
    Cough
         subjects affected / exposed
    18 / 41 (43.90%)
    4 / 43 (9.30%)
    6 / 21 (28.57%)
         occurrences all number
    23
    5
    9
    Pleural effusion
         subjects affected / exposed
    4 / 41 (9.76%)
    2 / 43 (4.65%)
    0 / 21 (0.00%)
         occurrences all number
    5
    2
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    2
    Productive cough
         subjects affected / exposed
    1 / 41 (2.44%)
    2 / 43 (4.65%)
    2 / 21 (9.52%)
         occurrences all number
    1
    2
    2
    Pulmonary embolism
         subjects affected / exposed
    2 / 41 (4.88%)
    5 / 43 (11.63%)
    0 / 21 (0.00%)
         occurrences all number
    2
    5
    0
    Rhinorrhoea
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 43 (0.00%)
    3 / 21 (14.29%)
         occurrences all number
    2
    0
    4
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    3 / 41 (7.32%)
    1 / 43 (2.33%)
    3 / 21 (14.29%)
         occurrences all number
    4
    1
    4
    Dysgeusia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    3 / 21 (14.29%)
         occurrences all number
    0
    1
    3
    Headache
         subjects affected / exposed
    10 / 41 (24.39%)
    8 / 43 (18.60%)
    4 / 21 (19.05%)
         occurrences all number
    20
    19
    8
    Paraesthesia
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 43 (2.33%)
    2 / 21 (9.52%)
         occurrences all number
    1
    1
    2
    Somnolence
         subjects affected / exposed
    5 / 41 (12.20%)
    2 / 43 (4.65%)
    3 / 21 (14.29%)
         occurrences all number
    6
    2
    4
    Tremor
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    2 / 21 (9.52%)
         occurrences all number
    0
    1
    2
    Eye disorders
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    2
    Eye pruritus
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    2
    Vision blurred
         subjects affected / exposed
    3 / 41 (7.32%)
    2 / 43 (4.65%)
    1 / 21 (4.76%)
         occurrences all number
    3
    2
    1
    Ocular discomfort
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    2
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    8 / 41 (19.51%)
    19 / 43 (44.19%)
    4 / 21 (19.05%)
         occurrences all number
    12
    38
    4
    Abdominal pain upper
         subjects affected / exposed
    5 / 41 (12.20%)
    8 / 43 (18.60%)
    4 / 21 (19.05%)
         occurrences all number
    8
    12
    4
    Ascites
         subjects affected / exposed
    0 / 41 (0.00%)
    7 / 43 (16.28%)
    1 / 21 (4.76%)
         occurrences all number
    0
    9
    1
    Colitis
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    10
    Diarrhoea
         subjects affected / exposed
    9 / 41 (21.95%)
    17 / 43 (39.53%)
    9 / 21 (42.86%)
         occurrences all number
    13
    23
    18
    Constipation
         subjects affected / exposed
    12 / 41 (29.27%)
    13 / 43 (30.23%)
    9 / 21 (42.86%)
         occurrences all number
    14
    24
    12
    Dry mouth
         subjects affected / exposed
    3 / 41 (7.32%)
    6 / 43 (13.95%)
    5 / 21 (23.81%)
         occurrences all number
    4
    8
    7
    Dyspepsia
         subjects affected / exposed
    0 / 41 (0.00%)
    3 / 43 (6.98%)
    3 / 21 (14.29%)
         occurrences all number
    0
    3
    5
    Flatulence
         subjects affected / exposed
    0 / 41 (0.00%)
    2 / 43 (4.65%)
    2 / 21 (9.52%)
         occurrences all number
    0
    2
    3
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 41 (0.00%)
    3 / 43 (6.98%)
    0 / 21 (0.00%)
         occurrences all number
    0
    3
    0
    Nausea
         subjects affected / exposed
    16 / 41 (39.02%)
    18 / 43 (41.86%)
    8 / 21 (38.10%)
         occurrences all number
    23
    30
    14
    Stomatitis
         subjects affected / exposed
    2 / 41 (4.88%)
    2 / 43 (4.65%)
    2 / 21 (9.52%)
         occurrences all number
    2
    4
    4
    Vomiting
         subjects affected / exposed
    12 / 41 (29.27%)
    15 / 43 (34.88%)
    6 / 21 (28.57%)
         occurrences all number
    14
    19
    9
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    3 / 21 (14.29%)
         occurrences all number
    0
    0
    3
    Erythema
         subjects affected / exposed
    3 / 41 (7.32%)
    0 / 43 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    3
    0
    2
    Hyperhidrosis
         subjects affected / exposed
    0 / 41 (0.00%)
    3 / 43 (6.98%)
    2 / 21 (9.52%)
         occurrences all number
    0
    4
    2
    Pruritus
         subjects affected / exposed
    4 / 41 (9.76%)
    2 / 43 (4.65%)
    8 / 21 (38.10%)
         occurrences all number
    4
    2
    8
    Rash pruritic
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 43 (0.00%)
    3 / 21 (14.29%)
         occurrences all number
    2
    0
    4
    Rash
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    3 / 21 (14.29%)
         occurrences all number
    1
    0
    5
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    6 / 41 (14.63%)
    5 / 43 (11.63%)
    4 / 21 (19.05%)
         occurrences all number
    8
    6
    6
    Back pain
         subjects affected / exposed
    8 / 41 (19.51%)
    3 / 43 (6.98%)
    8 / 21 (38.10%)
         occurrences all number
    13
    3
    15
    Bone pain
         subjects affected / exposed
    4 / 41 (9.76%)
    2 / 43 (4.65%)
    1 / 21 (4.76%)
         occurrences all number
    4
    2
    1
    Flank pain
         subjects affected / exposed
    3 / 41 (7.32%)
    0 / 43 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    4
    0
    0
    Muscle spasms
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 43 (2.33%)
    2 / 21 (9.52%)
         occurrences all number
    1
    1
    2
    Myalgia
         subjects affected / exposed
    2 / 41 (4.88%)
    3 / 43 (6.98%)
    3 / 21 (14.29%)
         occurrences all number
    2
    3
    3
    Pain in extremity
         subjects affected / exposed
    5 / 41 (12.20%)
    1 / 43 (2.33%)
    1 / 21 (4.76%)
         occurrences all number
    9
    1
    1
    Neck pain
         subjects affected / exposed
    2 / 41 (4.88%)
    1 / 43 (2.33%)
    3 / 21 (14.29%)
         occurrences all number
    2
    1
    3
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    1 / 41 (2.44%)
    3 / 43 (6.98%)
    2 / 21 (9.52%)
         occurrences all number
    1
    3
    2
    Metabolism and nutrition disorders
    Hyperkalaemia
         subjects affected / exposed
    3 / 41 (7.32%)
    0 / 43 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    3
    0
    2
    Decreased appetite
         subjects affected / exposed
    15 / 41 (36.59%)
    14 / 43 (32.56%)
    5 / 21 (23.81%)
         occurrences all number
    24
    22
    6
    Hypokalaemia
         subjects affected / exposed
    2 / 41 (4.88%)
    5 / 43 (11.63%)
    1 / 21 (4.76%)
         occurrences all number
    2
    7
    3
    Hypoalbuminaemia
         subjects affected / exposed
    2 / 41 (4.88%)
    4 / 43 (9.30%)
    0 / 21 (0.00%)
         occurrences all number
    2
    5
    0
    Hypomagnesaemia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    2 / 21 (9.52%)
         occurrences all number
    0
    1
    3
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    4 / 41 (9.76%)
    0 / 43 (0.00%)
    6 / 21 (28.57%)
         occurrences all number
    4
    0
    11
    Oral fungal infection
         subjects affected / exposed
    0 / 41 (0.00%)
    3 / 43 (6.98%)
    0 / 21 (0.00%)
         occurrences all number
    0
    3
    0
    Pneumonia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    1
    0
    2
    Respiratory tract infection
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    4 / 21 (19.05%)
         occurrences all number
    1
    0
    5
    Tooth infection
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    3
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 41 (2.44%)
    3 / 43 (6.98%)
    0 / 21 (0.00%)
         occurrences all number
    1
    3
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Apr 2017
    Inclusion Criteria Update
    14 Jun 2017
    Inclusion Criteria Update

    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
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