Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

    The EU Clinical Trials Register currently displays   44356   clinical trials with a EudraCT protocol, of which   7382   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Multiple Phase 1/2 Cohorts of Nivolumab Monotherapy or Nivolumab Combination Regimens Across Relapsed/Refractory Hematologic Malignancies

    Summary
    EudraCT number
    		 2018-001030-17
    Trial protocol
    		 GR   BE   PL   IT  
    Global end of trial date
    09 Jul 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    26 Jul 2025
    First version publication date
    26 Jul 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CA209-039
    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
    Global Submission Management, Clinical Trials, Bristol-Myers Squibb, mg-gsm-ct@bms.com
    Scientific contact
    Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, mg-gsm-ct@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
    09 Jul 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Jul 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To establish the tolerability of the combination of nivolumab and daratumumab in subjects with relapsed/refractory MM.
    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
    12 Aug 2012
    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
    Belgium: 2
    Country: Number of subjects enrolled
    France: 8
    Country: Number of subjects enrolled
    Greece: 10
    Country: Number of subjects enrolled
    Poland: 21
    Country: Number of subjects enrolled
    United States: 279
    Worldwide total number of subjects
    320
    EEA total number of subjects
    41
    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)
    197
    From 65 to 84 years
    110
    85 years and over
    13

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 For the phase 1 nivo monotherapy dose escalation included in this study, it was derived from CA209-003. It was concluded that 3mg/kg of nivolumab would be used for the dose expansion phase 2 of this study (CA209-039) based on the conclusions derived from CA209-003.

    Pre-assignment
    Screening details
    		 316 participants treated

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Nivolumab Monotherapy (expansion)
    Arm description
    		 3mg/kg of nivolumab
    Arm type
    		 Experimental

    Investigational medicinal product name
    nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1mg/kg or 3mg/kg

    Arm title
    		 Nivolumab + Ipilimumab
    Arm description
    		 3 mg/kg of nivolumab and 1 mg/kg of ipilimumab Q3W for 4 doses, followed by nivolumab alone at 3 mg/kg Q2W
    Arm type
    		 Experimental

    Investigational medicinal product name
    ipilimumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1mg/kg

    Investigational medicinal product name
    nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1mg/kg or 3mg/kg

    Arm title
    		 Nivolumab + Lirilumab
    Arm description
    		 3 mg/kg of nivolumab Q2W + 3 mg/kg of lirilumab Q4W
    Arm type
    		 Experimental

    Investigational medicinal product name
    nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1mg/kg or 3mg/kg

    Investigational medicinal product name
    lirilumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Emulsion for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    3mg/kg

    Arm title
    		 Nivolumab + Daratumumab_Cohort A1
    Arm description
    		 ND regimen: Nivolumab (240 mg up to cycle 6, then 480 mg) + Daratumumab (16 mg/Kg)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Daratumumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for concentrate for solution for infusion, Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100mg (20mg/mL) and 400mg (20mg/mL)

    Investigational medicinal product name
    nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    100mg (10mg/mL)

    Arm title
    		 Nivolumab + Daratumumab_Cohort A2
    Arm description
    		 ND-PD regimen; Nivolumab + Daratumumab + Pomalidomide + Dexamethasone
    Arm type
    		 Experimental

    Investigational medicinal product name
    nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    100mg (10mg/mL)

    Investigational medicinal product name
    Daratumumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for concentrate for solution for infusion, Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100mg (20mg/mL) and 400mg (20mg/mL)

    Investigational medicinal product name
    dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    2mg or 4mg

    Investigational medicinal product name
    dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    4mg/mL

    Investigational medicinal product name
    Pomalidomide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    1mg, 2mg, 3mg and 4mg

    Arm title
    		 Nivolumab + Daratumumab_Cohort B1
    Arm description
    		 ND regimen: Nivolumab (240 mg cycle 1, then 480 mg) + Daratumumab (16 mg/Kg)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Daratumumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for concentrate for solution for infusion, Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100mg (20mg/mL) and 400mg (20mg/mL)

    Investigational medicinal product name
    nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    100mg (10mg/mL)

    Arm title
    		 Nivolumab + Daratumumab_Cohort B2
    Arm description
    		 D regimen: Daratumumab alone
    Arm type
    		 Experimental

    Investigational medicinal product name
    Daratumumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for concentrate for solution for infusion, Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100mg (20mg/mL) and 400mg (20mg/mL)

    Investigational medicinal product name
    nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    100mg (10mg/mL)

    Number of subjects in period 1 [1]
    		Nivolumab Monotherapy (expansion) Nivolumab + Ipilimumab Nivolumab + Lirilumab Nivolumab + Daratumumab_Cohort A1 Nivolumab + Daratumumab_Cohort A2 Nivolumab + Daratumumab_Cohort B1 Nivolumab + Daratumumab_Cohort B2
    Started
    105
    65
    72
    6
    5
    41
    22
    Completed
    1
    40
    0
    1
    1
    7
    6
    Not completed
    104
    25
    72
    5
    4
    34
    16
         Other Reasons
    6
    -
    10
    -
    -
    1
    -
         Request to discontinue study treatment
    5
    -
    2
    -
    1
    2
    -
         Maximum clinical benefit
    11
    1
    7
    1
    -
    -
    -
         AE unrelated to study drug
    4
    3
    -
    -
    -
    -
    1
         No longer meets study criteria
    1
    -
    -
    -
    -
    -
    -
         Study Drug Toxicity
    14
    3
    -
    -
    -
    -
    1
         Withdrew consent
    1
    2
    1
    1
    -
    -
    -
         Disease Progression
    62
    16
    52
    3
    3
    31
    14
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Study includes subjects enrolled from CA209-003 which were used in CA209-039 dose finding.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Nivolumab Monotherapy (expansion)
    Reporting group description
    		 3mg/kg of nivolumab

    Reporting group title
    Nivolumab + Ipilimumab
    Reporting group description
    		 3 mg/kg of nivolumab and 1 mg/kg of ipilimumab Q3W for 4 doses, followed by nivolumab alone at 3 mg/kg Q2W

    Reporting group title
    Nivolumab + Lirilumab
    Reporting group description
    		 3 mg/kg of nivolumab Q2W + 3 mg/kg of lirilumab Q4W

    Reporting group title
    Nivolumab + Daratumumab_Cohort A1
    Reporting group description
    		 ND regimen: Nivolumab (240 mg up to cycle 6, then 480 mg) + Daratumumab (16 mg/Kg)

    Reporting group title
    Nivolumab + Daratumumab_Cohort A2
    Reporting group description
    		 ND-PD regimen; Nivolumab + Daratumumab + Pomalidomide + Dexamethasone

    Reporting group title
    Nivolumab + Daratumumab_Cohort B1
    Reporting group description
    		 ND regimen: Nivolumab (240 mg cycle 1, then 480 mg) + Daratumumab (16 mg/Kg)

    Reporting group title
    Nivolumab + Daratumumab_Cohort B2
    Reporting group description
    		 D regimen: Daratumumab alone

    Reporting group values
    		 Nivolumab Monotherapy (expansion) Nivolumab + Ipilimumab Nivolumab + Lirilumab Nivolumab + Daratumumab_Cohort A1 Nivolumab + Daratumumab_Cohort A2 Nivolumab + Daratumumab_Cohort B1 Nivolumab + Daratumumab_Cohort B2 Total
    Number of subjects
    		 105 65 72 6 5 41 22 316
    Age Categorical
    Units: Participants
        <=18 years
    		 0 0 0 0 0 0 0 0
        Between 18 and 65 years
    		 66 46 52 3 2 16 11 196
        >=65 years
    		 39 19 20 3 3 25 11 120
    Sex: Female, Male
    Units: Participants
        Female
    		 45 28 26 3 1 24 8 135
        Male
    		 60 37 46 3 4 17 14 181
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0 0 0 0
        Asian
    		 2 1 0 0 0 0 0 3
        Native Hawaiian or Other Pacific Islander
    		 1 0 0 0 0 0 0 1
        Black or African American
    		 11 5 7 0 0 1 2 26
        White
    		 89 58 63 5 5 36 19 275
        More than one race
    		 0 0 0 0 0 0 0 0
        Unknown or Not Reported
    		 2 1 2 1 0 4 1 11
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 13 3 2 0 0 2 0 20
        Not Hispanic or Latino
    		 91 62 69 6 5 27 17 277
        Unknown or Not Reported
    		 1 0 1 0 0 12 5 19

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Nivolumab Monotherapy (expansion)
    Reporting group description
    		 3mg/kg of nivolumab

    Reporting group title
    Nivolumab + Ipilimumab
    Reporting group description
    		 3 mg/kg of nivolumab and 1 mg/kg of ipilimumab Q3W for 4 doses, followed by nivolumab alone at 3 mg/kg Q2W

    Reporting group title
    Nivolumab + Lirilumab
    Reporting group description
    		 3 mg/kg of nivolumab Q2W + 3 mg/kg of lirilumab Q4W

    Reporting group title
    Nivolumab + Daratumumab_Cohort A1
    Reporting group description
    		 ND regimen: Nivolumab (240 mg up to cycle 6, then 480 mg) + Daratumumab (16 mg/Kg)

    Reporting group title
    Nivolumab + Daratumumab_Cohort A2
    Reporting group description
    		 ND-PD regimen; Nivolumab + Daratumumab + Pomalidomide + Dexamethasone

    Reporting group title
    Nivolumab + Daratumumab_Cohort B1
    Reporting group description
    		 ND regimen: Nivolumab (240 mg cycle 1, then 480 mg) + Daratumumab (16 mg/Kg)

    Reporting group title
    Nivolumab + Daratumumab_Cohort B2
    Reporting group description
    		 D regimen: Daratumumab alone

    Subject analysis set title
    Cohort A-1
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    ND Regimen Each cycle is 28 days Nivolumab: Cycle 1: 240 mg iv Day 15 Cycle 2-6: 240 mg iv Days 1, 15 Cycle 7 & beyond: 480 mg iv Day 1 Daratumumab: Cycle 1-2: 16 mg/kg iv Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg iv Days 1, 15 Cycle 7 & beyond: 16 mg/kg iv Day 1 Pomalidomide: 4 mg po daily (Days 1-21) of each 28-day cycle Dexamethasone: Weeks without daratumumab dosing 40 mg po per day (Days 1, 8, 15, 22) of each 28-day cycle for subjects 75 years old 20 mg po per day (Days 1, 8, 15, 22) of each 28-day cycle for subjects > 75 years old

    Subject analysis set title
    Cohort B-1
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    ND Regimen Each cycle is 28 days Nivolumab: Cycle 1: 240 mg iv Day 15 Cycle 2 & beyond: 480 mg iv Day 1 Daratumumab: Cycle 1*-2: 16 mg/kg iv Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg iv Days 1, 15 Cycle 7 & beyond: 16 mg/kg iv Day 1

    Subject analysis set title
    Cohort B-2
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    D Monotherapy Regimen Each cycle is 28 days Daratumumab: Cycle 1*-2: 16 mg/kg iv Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg iv Days 1, 15 Cycle 7 & beyond: 16 mg/kg iv Day 1

    Subject analysis set title
    Cohort A-1
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    ND Regimen Each cycle is 28 days Nivolumab: Cycle 1: 240 mg iv Day 15 Cycle 2-6: 240 mg iv Days 1, 15 Cycle 7 & beyond: 480 mg iv Day 1 Daratumumab: Cycle 1-2: 16 mg/kg iv Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg iv Days 1, 15 Cycle 7 & beyond: 16 mg/kg iv Day 1 Pomalidomide: 4 mg po daily (Days 1-21) of each 28-day cycle Dexamethasone: Weeks without daratumumab dosing 40 mg po per day (Days 1, 8, 15, 22) of each 28-day cycle for subjects 75 years old 20 mg po per day (Days 1, 8, 15, 22) of each 28-day cycle for subjects > 75 years old

    Subject analysis set title
    Cohort A-2
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    ND-Pd Regimen Each cycle is 28 days Nivolumab: Cycle 1: 240 mg iv Day 15 Cycle 2-6: 240 mg iv Days 1, 15 Cycle 7 & beyond: 480 mg iv Day 1 Daratumumab: Cycle 1-2: 16 mg/kg iv Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg iv Days 1, 15 Cycle 7 & beyond: 16 mg/kg iv Day 1

    Subject analysis set title
    Cohort B-1
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    ND Regimen Each cycle is 28 days Nivolumab: Cycle 1: 240 mg iv Day 15 Cycle 2 & beyond: 480 mg iv Day 1 Daratumumab: Cycle 1*-2: 16 mg/kg iv Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg iv Days 1, 15 Cycle 7 & beyond: 16 mg/kg iv Day 1

    Subject analysis set title
    Cohort B-2
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    D Monotherapy Regimen Each cycle is 28 days Daratumumab: Cycle 1*-2: 16 mg/kg iv Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg iv Days 1, 15 Cycle 7 & beyond: 16 mg/kg iv Day 1

    Subject analysis set title
    Cohort A-2
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    ND-Pd Regimen Each cycle is 28 days Nivolumab: Cycle 1: 240 mg iv Day 15 Cycle 2-6: 240 mg iv Days 1, 15 Cycle 7 & beyond: 480 mg iv Day 1 Daratumumab: Cycle 1-2: 16 mg/kg iv Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg iv Days 1, 15 Cycle 7 & beyond: 16 mg/kg iv Day 1

    Subject analysis set title
    Cohort B-1
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    ND Regimen Each cycle is 28 days Nivolumab: Cycle 1: 240 mg iv Day 15 Cycle 2 & beyond: 480 mg iv Day 1 Daratumumab: Cycle 1*-2: 16 mg/kg iv Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg iv Days 1, 15 Cycle 7 & beyond: 16 mg/kg iv Day 1

    Primary: Number of participants that experienced drug related Grade 3-4 AEs

    		 Close Top of page
    End point title
    		 Number of participants that experienced drug related Grade 3-4 AEs [1] [2]
    End point description
    Number and percent of participants that experienced drug related Grade 3-4 AEs occurring up to 100 days after the last dose of study drug.
    End point type
    Primary
    End point timeframe
    Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
    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 further statistical analysis done for this endpoint
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab Monotherapy (expansion) Nivolumab + Ipilimumab Nivolumab + Lirilumab
    Number of subjects analysed
    105
    65
    72
    Units: Participants
    19
    18
    0
    No statistical analyses for this end point

    Primary: Number of participants that experienced drug related Grade 3-4 SAEs

    		 Close Top of page
    End point title
    		 Number of participants that experienced drug related Grade 3-4 SAEs [3] [4]
    End point description
    Number and percent of participants that experienced drug related Grade 3-4 SAEs occurring up to 100 days after the last dose of study drug.
    End point type
    Primary
    End point timeframe
    Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
    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: no further statistical analysis done for this endpoint
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab Monotherapy (expansion) Nivolumab + Ipilimumab Nivolumab + Lirilumab
    Number of subjects analysed
    105
    65
    72
    Units: Participants
    28
    8
    3
    No statistical analyses for this end point

    Primary: Number of participants with clinical laboratory abnormalities by worst toxicity grade - Liver

    		 Close Top of page
    End point title
    		 Number of participants with clinical laboratory abnormalities by worst toxicity grade - Liver [5] [6]
    End point description
    Number and percent of participants that experienced drug related Grade 3-4 AEs occurring up to 100 days after the last dose of study drug.
    End point type
    Primary
    End point timeframe
    Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
    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: no further statistical analysis done for this endpoint
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab Monotherapy (expansion) Nivolumab + Ipilimumab Nivolumab + Lirilumab
    Number of subjects analysed
    105
    65
    72
    Units: Participants
        ALT OR AST > 3XULN
    3
    1
    4
        ALT OR AST > 5XULN
    1
    0
    2
        ALT OR AST > 10XULN
    1
    0
    1
        ALT OR AST > 20XULN
    1
    0
    0
        TOTAL BILIRUBIN > 2XULN
    1
    1
    2
        ALT/AST > 3xULN & Bilirubin > 2xULN in 1 day
    1
    0
    1
        ALT/AST > 3xULN & Bilirubin > 2xULN in 30 days
    1
    0
    1
    No statistical analyses for this end point

    Primary: Number of participants with clinical laboratory abnormalities by worst toxicity grade - Thyroid

    		 Close Top of page
    End point title
    		 Number of participants with clinical laboratory abnormalities by worst toxicity grade - Thyroid [7] [8]
    End point description
    End point type
    Primary
    End point timeframe
    Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
    Notes
    [7] - 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 further statistical analysis done for this endpoint
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab Monotherapy (expansion) Nivolumab + Ipilimumab Nivolumab + Lirilumab
    Number of subjects analysed
    83
    47
    72
    Units: Participants
        TSH > ULN
    14
    19
    15
        TSH > ULN WITH TSH <= ULN AT BASELINE
    11
    13
    9
        TSH >ULN WITH ATLEAST ONE FT3/FT4 TEST VALUE <LLN
    0
    7
    1
        TSH >ULN WITH ALL OTHER FT3/FT4 TEST VALUES ≥ LLN
    1
    1
    1
        TSH > ULN WITH FT3/FT4 TEST MISSING
    13
    11
    13
        TSH < LLN
    8
    6
    6
        TSH <LLN WITH TSH ≥ LLN AT BASELINE
    5
    6
    4
        TSH <LLN WITH ATLEAST ONE FT3/FT4 TEST VALUE > ULN
    0
    1
    1
        TSH <LLN WITH ALL OTHER FT3/FT4 TEST VALUES ≤ ULN
    0
    0
    0
        TSH < LLN WITH FT3/FT4 TEST MISSING
    8
    5
    5
    No statistical analyses for this end point

    Primary: Number of participants that experienced drug-related grade 3-4 AEs in the Nivolumab + Daratumumab Cohort

    		 Close Top of page
    End point title
    		 Number of participants that experienced drug-related grade 3-4 AEs in the Nivolumab + Daratumumab Cohort [9] [10]
    End point description
    End point type
    Primary
    End point timeframe
    approximately up to 4 years
    Notes
    [9] - 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 further statistical analysis done for this endpoint
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab + Daratumumab_Cohort A1 Nivolumab + Daratumumab_Cohort A2 Nivolumab + Daratumumab_Cohort B1 Nivolumab + Daratumumab_Cohort B2
    Number of subjects analysed
    6
    5
    41
    22
    Units: Participants
    2
    5
    13
    2
    No statistical analyses for this end point

    Primary: Number of participants that experienced drug-related grade 3-4 SAEs in the Nivolumab + Daratumumab Cohort

    		 Close Top of page
    End point title
    		 Number of participants that experienced drug-related grade 3-4 SAEs in the Nivolumab + Daratumumab Cohort [11] [12]
    End point description
    End point type
    Primary
    End point timeframe
    approximately up to 4 years
    Notes
    [11] - 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 further statistical analysis done for this endpoint
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab + Daratumumab_Cohort A1 Nivolumab + Daratumumab_Cohort A2 Nivolumab + Daratumumab_Cohort B1 Nivolumab + Daratumumab_Cohort B2
    Number of subjects analysed
    6
    5
    41
    22
    Units: Participants
    2
    4
    10
    6
    No statistical analyses for this end point

    Primary: Number of participants with clinical laboratory abnormalities by worst toxicity grade in the Nivolumab + Daratumumab Cohort - Hematology

    		 Close Top of page
    End point title
    		 Number of participants with clinical laboratory abnormalities by worst toxicity grade in the Nivolumab + Daratumumab Cohort - Hematology [13] [14]
    End point description
    End point type
    Primary
    End point timeframe
    approximately up to 4 years
    Notes
    [13] - 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 further statistical analysis done for this endpoint
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab + Daratumumab_Cohort A1 Nivolumab + Daratumumab_Cohort A2 Nivolumab + Daratumumab_Cohort B1 Nivolumab + Daratumumab_Cohort B2
    Number of subjects analysed
    6
    5
    41
    22
    Units: Participants
        Hemoglobin|Grade 0
    0
    0
    3
    1
        Platelet count|Grade 0
    3
    1
    19
    8
        Leukocytes|Grade 0
    2
    0
    10
    5
        Lymphocytes (Absolute)|Grade 0
    3
    0
    6
    3
        Absolute Neutrophil Count|Grade 0
    3
    0
    14
    10
        Hemoglobin|Grade 1
    2
    2
    13
    13
        Platelet count|Grade 1
    2
    3
    11
    9
        Leukocytes|Grade 1
    1
    0
    6
    9
        Lymphocytes (Absolute)|Grade 1
    0
    0
    9
    5
        Absolute Neutrophil Count|Grade 1
    2
    0
    8
    6
        Hemoglobin|Grade 2
    2
    2
    20
    5
        Platelet count|Grade 2
    0
    1
    3
    3
        Leukocytes|Grade 2
    2
    2
    15
    5
        Lymphocytes (Absolute)|Grade 2
    0
    0
    9
    7
        Absolute Neutrophil Count|Grade 2
    0
    0
    6
    6
        Hemoglobin|Grade 3
    2
    1
    5
    2
        Platelet count|Grade 3
    0
    0
    3
    0
        Leukocytes|Grade 3
    0
    2
    9
    2
        Lymphocytes (Absolute)|Grade 3
    2
    3
    15
    5
        Absolute Neutrophil Count|Grade 3
    1
    3
    9
    0
        Hemoglobin|Grade 4
    0
    0
    0
    0
        Platelet count|Grade 4
    1
    0
    5
    1
        Leukocytes|Grade 4
    1
    1
    1
    0
        Lymphocytes (Absolute)|Grade 4
    1
    2
    2
    1
        Absolute Neutrophil Count|Grade 4
    0
    2
    4
    0
    No statistical analyses for this end point

    Primary: Number of participants with clinical laboratory abnormalities by worst toxicity grade in the Nivolumab + Daratumumab Cohort - Liver

    		 Close Top of page
    End point title
    		 Number of participants with clinical laboratory abnormalities by worst toxicity grade in the Nivolumab + Daratumumab Cohort - Liver [15] [16]
    End point description
    End point type
    Primary
    End point timeframe
    approximately up to 4 years
    Notes
    [15] - 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 further statistical analysis done for this endpoint
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab + Daratumumab_Cohort A1 Nivolumab + Daratumumab_Cohort A2 Nivolumab + Daratumumab_Cohort B1 Nivolumab + Daratumumab_Cohort B2
    Number of subjects analysed
    6
    5
    41
    22
    Units: Participants
        ALT or AST >3xULN
    0
    0
    0
    0
        ALT or AST >5xULN
    1
    3
    9
    0
        ALT or AST >10xULN
    1
    3
    9
    0
        ALT or AST >20xULN
    1
    3
    9
    0
        Total Bilirubin > 2xULN
    1
    3
    9
    0
        ALT/AST > 3xULN & Bilirubin > 2xULN in 1 days
    1
    3
    9
    0
        ALT/AST > 3xULN & Bilirubin > 2xULN in 30 days
    1
    3
    9
    0
    No statistical analyses for this end point

    Primary: Number of participants with clinical laboratory abnormalities by worst toxicity grade in the Nivolumab + Daratumumab Cohort - Thyroid

    		 Close Top of page
    End point title
    		 Number of participants with clinical laboratory abnormalities by worst toxicity grade in the Nivolumab + Daratumumab Cohort - Thyroid [17] [18]
    End point description
    End point type
    Primary
    End point timeframe
    approximately up to 4 years
    Notes
    [17] - 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 further statistical analysis done for this endpoint
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab + Daratumumab_Cohort A1 Nivolumab + Daratumumab_Cohort A2 Nivolumab + Daratumumab_Cohort B1 Nivolumab + Daratumumab_Cohort B2
    Number of subjects analysed
    6
    5
    38
    19
    Units: Participants
        TSH>ULN
    3
    1
    8
    3
        TSH > ULN WITH TSH <= ULN AT BASELINE
    1
    1
    7
    2
        TSH >ULN WITH ATLEAST ONE FT3/FT4 TEST VALUE <LLN
    1
    0
    1
    0
        TSH >ULN WITH ALL OTHER FT3/FT4 TEST VALUES ≥ LLN
    0
    0
    5
    2
        WITH FT3/FT4 TEST MISSING
    2
    1
    2
    1
        TSH < LLN
    0
    2
    2
    2
        TSH < LLN WITH TSH >= LLN AT BASELINE
    0
    2
    2
    1
        TSH <LLN WITH ATLEAST ONE FT3/FT4 TEST VALUE > ULN
    0
    0
    0
    0
        TSH <LLN WITH ALL OTHER FT3/FT4 TEST VALUES ≤ ULN
    0
    0
    1
    2
        TSH < LLN WITH FT3/FT4 TEST MISSING
    0
    2
    1
    0
    No statistical analyses for this end point

    Secondary: Best Overall Response

    		 Close Top of page
    End point title
    		 Best Overall Response [19]
    End point description
    the best response designation over the study as a whole, recorded between the date of first dose and the last efficacy assessment prior to subsequent therapy. Measured in Complete Response and Partial Response
    End point type
    Secondary
    End point timeframe
    Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab Monotherapy (expansion) Nivolumab + Ipilimumab Nivolumab + Lirilumab
    Number of subjects analysed
    77
    58
    62
    Units: Percentage of participants
    number (confidence interval 95%)
        Complete Response
    10.4 (4.6 to 19.4)
    13.8 (6.1 to 25.4)
    9.7 (3.6 to 19.9)
        Partial Response
    33.8 (23.4 to 45.4)
    34.5 (22.5 to 48.1)
    29.0 (18.2 to 41.9)
    No statistical analyses for this end point

    Secondary: Best Overall Response - Multiple Myeloma Group

    		 Close Top of page
    End point title
    		 Best Overall Response - Multiple Myeloma Group [20]
    End point description
    the best response designation over the study as a whole, recorded between the date of first dose and the last efficacy assessment prior to subsequent therapy. here "99999 and -99999" = NA
    End point type
    Secondary
    End point timeframe
    Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab Monotherapy (expansion) Nivolumab + Ipilimumab Nivolumab + Lirilumab
    Number of subjects analysed
    27
    7
    10
    Units: Percentage
    number (confidence interval 95%)
        Complete Remission
    3.7 (0.1 to 19.0)
    0 (0 to 41.0)
    0 (0 to 30.8)
        Partial Remission
    0 (0.0 to 12.8)
    0 (0 to 41.0)
    0 (0 to 30.8)
        Very Good Partial Response
    0 (0.0 to 12.8)
    0 (0 to 41.0)
    99999 (-99999 to 99999)
        Stringent Compete Response
    0 (0.0 to 12.8)
    0 (0 to 41.0)
    99999 (-99999 to 99999)
    No statistical analyses for this end point

    Secondary: Duration of Response - Multiple Myeloma Group

    		 Close Top of page
    End point title
    		 Duration of Response - Multiple Myeloma Group [21]
    End point description
    the best response designation over the study as a whole, recorded between the date of first dose and the last efficacy assessment prior to subsequent therapy. Measured in Complete Response and Partial Response here "99999 and -99999" = NA
    End point type
    Secondary
    End point timeframe
    Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab Monotherapy (expansion) Nivolumab + Ipilimumab Nivolumab + Lirilumab
    Number of subjects analysed
    1
    0 [22]
    0 [23]
    Units: Months
        median (full range (min-max))
    99999 (99999 to 99999)
    ( to )
    ( to )
    Notes
    [22] - no subjects analyzed
    [23] - no subjects analyzed
    No statistical analyses for this end point

    Secondary: Progression Free Survival

    		 Close Top of page
    End point title
    		 Progression Free Survival [24]
    End point description
    Progression free survival (PFS) is defined as the time between date of randomization and date of progression or death, whichever occurs first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Subjects who did not progress or die were censored on the date of their last efficacy assessment.
    End point type
    Secondary
    End point timeframe
    From date of randomization to date of progression or death, whichever occurs first (up to approximately 24 months)
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab Monotherapy (expansion) Nivolumab + Ipilimumab Nivolumab + Lirilumab
    Number of subjects analysed
    104
    65
    72
    Units: Months
        median (confidence interval 95%)
    6.24 (3.48 to 9.79)
    6.93 (2.79 to 19.15)
    3.02 (1.84 to 5.52)
    No statistical analyses for this end point

    Secondary: Duration of Response

    		 Close Top of page
    End point title
    		 Duration of Response [25]
    End point description
    the best response designation over the study as a whole, recorded between the date of first dose and the last efficacy assessment prior to subsequent therapy. Measured in Complete Remission and Partial Remission
    End point type
    Secondary
    End point timeframe
    Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to approximately 37 months Nivo Liri: approximately up to 4 years 1 month
    Notes
    [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab Monotherapy (expansion) Nivolumab + Ipilimumab Nivolumab + Lirilumab
    Number of subjects analysed
    34
    28
    24
    Units: Months
        median (full range (min-max))
    22.83 (0.0 to 48.6)
    24.84 (0.0 to 36.5)
    19.38 (0.0 to 45.5)
    No statistical analyses for this end point

    Secondary: Progression Free Survival Rate

    		 Close Top of page
    End point title
    		 Progression Free Survival Rate [26]
    End point description
    The percentage of participants remaining progression free at the specified timepoints (up to 48 Months) here "99999 and -99999" = NA
    End point type
    Secondary
    End point timeframe
    From randomization to the specified timepoints (up to 48 months)
    Notes
    [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab Monotherapy (expansion) Nivolumab + Ipilimumab Nivolumab + Lirilumab
    Number of subjects analysed
    104
    65
    72
    Units: Percentage of Participants
    number (confidence interval 95%)
        2 Months
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    58.0 (45.3 to 68.8)
        4 Months
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    42.4 (30.4 to 54.0)
        6 Months
    50.5 (39.8 to 60.3)
    51.5 (38.1 to 63.4)
    34.3 (23.0 to 45.8)
        9 Months
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    32.5 (21.4 to 44.0)
        12 Months
    34.8 (24.2 to 45.5)
    45.3 (32.0 to 57.7)
    99999 (99999 to 99999)
        18 Months
    31.0 (20.7 to 42.0)
    40.1 (26.8 to 53.1)
    99999 (99999 to 99999)
        24 Months
    20.3 (11.1 to 31.5)
    30.9 (18.0 to 44.9)
    99999 (99999 to 99999)
        36 Months
    15.8 (7.6 to 26.8)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
        48 Months
    13.2 (5.6 to 24.1)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Number of Participants with PD-L1 expression

    		 Close Top of page
    End point title
    		 Number of Participants with PD-L1 expression [27]
    End point description
    Number of Participants with PD-L1 expression in the following categories -baseline PD-L1 expression ≥ 1% -baseline PD-L1 expression < 1% -without PD-L1 quantifiable at baseline
    End point type
    Secondary
    End point timeframe
    At baseline (prior to start of study treatment)
    Notes
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab Monotherapy (expansion) Nivolumab + Ipilimumab Nivolumab + Lirilumab
    Number of subjects analysed
    105
    65
    72
    Units: Number of Participants
        Baseline PD-L1 expression ≥ 1%
    25
    26
    16
        Baseline PD-L1 expression < 1%
    16
    14
    20
        PD-L1 not quantifiable at baseline
    64
    25
    36
    No statistical analyses for this end point

    Secondary: Overall Survival

    		 Close Top of page
    End point title
    		 Overall Survival [28]
    End point description
    The percentage of participants remaining alive. Median values are computed using Kaplan-Meier method here "99999 and -99999" = NA
    End point type
    Secondary
    End point timeframe
    Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to3 years Nivo Liri: approximately up to 4 years 1 month
    Notes
    [28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab Monotherapy (expansion) Nivolumab + Ipilimumab Nivolumab + Lirilumab
    Number of subjects analysed
    104
    65
    72
    Units: Months
        median (confidence interval 95%)
    52.57 (29.0 to 99999)
    30.39 (13.24 to 99999)
    14.95 (9.36 to 34.23)
    No statistical analyses for this end point

    Secondary: Percentage change from baseline in the Modified Severity Weighted Assessment Tool (mSWAT) score

    		 Close Top of page
    End point title
    		 Percentage change from baseline in the Modified Severity Weighted Assessment Tool (mSWAT) score [29]
    End point description
    mSWAT is a scoring technique involving the direct assessment of the percentage of body-surface-area (BSA) affected by skin lesions. There are 12 body regions (each one assigned a different percentage of BSA). For each body region, the assigned BSA percentage is multiplied by a factor weighing the type and severity of lesion observed (patch= x1, plaque = x2, tumor= x4). The sum of the individual body region sub-scores is then summed to generate the final mSWAT score, which ranges from 0 (best outcome) to 400 (worst outcome). here "99999 and -99999" = NA
    End point type
    Secondary
    End point timeframe
    From baseline (last measurement before start of study treatment) to last available measurement after start of study treatment (88 weeks for Nivo mono, 93 weeks for nivo+ipi, 25 weeks for nivo+liri)
    Notes
    [29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab Monotherapy (expansion) Nivolumab + Ipilimumab Nivolumab + Lirilumab
    Number of subjects analysed
    1
    1
    1
    Units: Percent of change from baseline
        arithmetic mean (standard deviation)
    8.70 ( 99999 )
    63.03 ( 99999 )
    -39.49 ( 99999 )
    No statistical analyses for this end point

    Secondary: Time to MRD Negativity Status in the Nivolumab + Daratumumab Cohort

    		 Close Top of page
    End point title
    		 Time to MRD Negativity Status in the Nivolumab + Daratumumab Cohort
    End point description
    Time to MRD Negativity status in specific NGS and NGF sensitivity levels here "99999 and -99999" = NA
    End point type
    Secondary
    End point timeframe
    approximately up to 4 years
    End point values
    		 Cohort A-1 Cohort B-1 Cohort B-2
    Number of subjects analysed
    1
    6
    4
    Units: Months
    arithmetic mean (standard deviation)
        NGS sensitivity level=10e-4
    3.02 ( 99999 )
    3.60 ( 2.409 )
    2.83 ( 99999 )
        NGS sensitivity level=10e-5
    3.02 ( 99999 )
    5.45 ( 4.788 )
    99999 ( 99999 )
        NGS sensitivity level=10e-6
    30.85 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        NGF sensitivity level=10e-4
    99999 ( 99999 )
    2.94 ( 0.230 )
    4.20 ( 2.766 )
        NGF sensitivity level=10e-5
    99999 ( 99999 )
    6.97 ( 6.776 )
    99999 ( 99999 )
        NGF sensitivity level=10e-6
    99999 ( 99999 )
    12.30 ( 3.508 )
    99999 ( 99999 )
    No statistical analyses for this end point

    Secondary: Objective Response Rate in the Nivolumab + Daratumumab Cohort

    		 Close Top of page
    End point title
    		 Objective Response Rate in the Nivolumab + Daratumumab Cohort
    End point description
    End point type
    Secondary
    End point timeframe
    approximately up to 4 years
    End point values
    		 Cohort A-1 Cohort A-2 Cohort B-1 Cohort B-2
    Number of subjects analysed
    6
    7
    43
    22
    Units: Percentage
        number (confidence interval 95%)
    66.7 (22.3 to 95.7)
    71.4 (29.0 to 93.3)
    51.2 (35.5 to 66.7)
    36.4 (17.2 to 59.3)
    No statistical analyses for this end point

    Secondary: Duration of response in the Nivolumab + Daratumumab Cohort

    		 Close Top of page
    End point title
    		 Duration of response in the Nivolumab + Daratumumab Cohort
    End point description
    here "99999 and -99999" = NA
    End point type
    Secondary
    End point timeframe
    approximately up to 4 years
    End point values
    		 Cohort A-1 Cohort A-2 Cohort B-1 Cohort B-2
    Number of subjects analysed
    6
    7
    43
    22
    Units: Months
        median (confidence interval 95%)
    99999 (6.47 to 99999)
    99999 (9.30 to 99999)
    6.70 (3.71 to 14.29)
    12.98 (2.20 to 99999)
    No statistical analyses for this end point

    Secondary: Progression Free Survival in the Nivolumab + Daratumumab Cohort

    		 Close Top of page
    End point title
    		 Progression Free Survival in the Nivolumab + Daratumumab Cohort
    End point description
    here "99999 and -99999" = NA
    End point type
    Secondary
    End point timeframe
    approximately up to 4 years
    End point values
    		 Cohort A-1 Cohort A-2 Cohort B-1 Cohort B-2
    Number of subjects analysed
    6
    7
    43
    22
    Units: Months
        median (confidence interval 95%)
    7.56 (3.19 to 99999)
    16.95 (-99999 to 99999)
    7.49 (4.67 to 9.46)
    7.01 (2.96 to 12.94)
    No statistical analyses for this end point

    Secondary: Cmax in the Nivolumab + Daratumumab Cohort

    		 Close Top of page
    End point title
    		 Cmax in the Nivolumab + Daratumumab Cohort [30]
    End point description
    Maximum observed serum concentration
    End point type
    Secondary
    End point timeframe
    approximately up to 4 years
    Notes
    [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab + Daratumumab_Cohort A1 Nivolumab + Daratumumab_Cohort A2 Nivolumab + Daratumumab_Cohort B1 Nivolumab + Daratumumab_Cohort B2
    Number of subjects analysed
    0 [31]
    0 [32]
    0 [33]
    0 [34]
    Units: ug/mL
        arithmetic mean (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [31] - Data Not Collected
    [32] - Data Not Collected
    [33] - Data Not Collected
    [34] - Data Not Collected
    No statistical analyses for this end point

    Secondary: Tmax in the Nivolumab + Daratumumab Cohort

    		 Close Top of page
    End point title
    		 Tmax in the Nivolumab + Daratumumab Cohort [35]
    End point description
    Time of maximum observed serum concentration
    End point type
    Secondary
    End point timeframe
    approximately up to 4 years
    Notes
    [35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab + Daratumumab_Cohort A1 Nivolumab + Daratumumab_Cohort A2 Nivolumab + Daratumumab_Cohort B1 Nivolumab + Daratumumab_Cohort B2
    Number of subjects analysed
    0 [36]
    0 [37]
    0 [38]
    0 [39]
    Units: weeks
        arithmetic mean (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [36] - Data Not Collected
    [37] - Data Not Collected
    [38] - Data Not Collected
    [39] - Data Not Collected
    No statistical analyses for this end point

    Secondary: Cmin in the Nivolumab + Daratumumab Cohort

    		 Close Top of page
    End point title
    		 Cmin in the Nivolumab + Daratumumab Cohort [40]
    End point description
    Serum concentration achieved at the end of dosing interval (trough concentration)
    End point type
    Secondary
    End point timeframe
    approximately up to 4 years
    Notes
    [40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab + Daratumumab_Cohort A1 Nivolumab + Daratumumab_Cohort A2 Nivolumab + Daratumumab_Cohort B1 Nivolumab + Daratumumab_Cohort B2
    Number of subjects analysed
    0 [41]
    0 [42]
    0 [43]
    0 [44]
    Units: ug/mL
        arithmetic mean (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [41] - Data Not Collected
    [42] - Data Not Collected
    [43] - Data Not Collected
    [44] - Data Not Collected
    No statistical analyses for this end point

    Secondary: AUC (0-T) in the Nivolumab + Daratumumab Cohort

    		 Close Top of page
    End point title
    		 AUC (0-T) in the Nivolumab + Daratumumab Cohort [45]
    End point description
    Area under the plasma concentration-time curve from time zero to the last time of the last quantifiable concentration
    End point type
    Secondary
    End point timeframe
    approximately up to 4 years
    Notes
    [45] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab + Daratumumab_Cohort A1 Nivolumab + Daratumumab_Cohort A2 Nivolumab + Daratumumab_Cohort B1 Nivolumab + Daratumumab_Cohort B2
    Number of subjects analysed
    0 [46]
    0 [47]
    0 [48]
    0 [49]
    Units: ug/mL
        arithmetic mean (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [46] - Data Not Collected
    [47] - Data Not Collected
    [48] - Data Not Collected
    [49] - Data Not Collected
    No statistical analyses for this end point

    Secondary: AUC (TAU) in the Nivolumab + Daratumumab Cohort

    		 Close Top of page
    End point title
    		 AUC (TAU) in the Nivolumab + Daratumumab Cohort [50]
    End point description
    Area under the concentration-time curve in one dosing interval
    End point type
    Secondary
    End point timeframe
    approximately up to 4 years
    Notes
    [50] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no further statistical analysis done for this endpoint
    End point values
    		 Nivolumab + Daratumumab_Cohort A1 Nivolumab + Daratumumab_Cohort A2 Nivolumab + Daratumumab_Cohort B1 Nivolumab + Daratumumab_Cohort B2
    Number of subjects analysed
    0 [51]
    0 [52]
    0 [53]
    0 [54]
    Units: ug/mL
        arithmetic mean (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [51] - Data Not Collected
    [52] - Data Not Collected
    [53] - Data Not Collected
    [54] - Data Not Collected
    No statistical analyses for this end point

    Secondary: End of Infusion Nivolumab concentration levels in the Nivolumab + Daratumumab Cohort

    		 Close Top of page
    End point title
    		 End of Infusion Nivolumab concentration levels in the Nivolumab + Daratumumab Cohort
    End point description
    Serum concentration achieved at the end of study drug infusion here "99999 and -99999" = NA
    End point type
    Secondary
    End point timeframe
    Measurements collected at cycles 1, 2, 3, 5, 7, and 11; each cycle is 28 days
    End point values
    		 Cohort A-1 Cohort A-2 Cohort B-1
    Number of subjects analysed
    6
    5
    41
    Units: ug/mL
    arithmetic mean (standard deviation)
        Cycle 1
    57.28 ( 6.78 )
    99999 ( 99999 )
    69.59 ( 18.79 )
        Cycle 2
    99999 ( 99999 )
    99999 ( 99999 )
    175.73 ( 88.94 )
        Cycle 3
    105.14 ( 31.41 )
    99999 ( 99999 )
    193.38 ( 69.74 )
        Cycle 5
    99999 ( 99999 )
    99999 ( 99999 )
    208.14 ( 58.38 )
        Cycle 7
    227.75 ( 26.79 )
    206.00 ( 99999 )
    193.00 ( 70.06 )
        Cycle 11
    99999 ( 99999 )
    206.00 ( 99999 )
    212.00 ( 38.20 )
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month Nivo Dara: approximately 4 years
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.0
    Reporting groups
    Reporting group title
    Nivolumab Monotherapy (expansion)
    Reporting group description
    		 3mg/kg of nivolumab

    Reporting group title
    Nivolumab + Lirilumab
    Reporting group description
    		 3 mg/kg of nivolumab Q2W + 3 mg/kg of lirilumab Q4W

    Reporting group title
    Nivolumab + Daratumumab_Cohort B2
    Reporting group description
    		 D regimen: Daratumumab alone

    Reporting group title
    Nivolumab + Daratumumab_Cohort A2
    Reporting group description
    		 ND-PD regimen; Nivolumab + Daratumumab + Pomalidomide + Dexamethasone

    Reporting group title
    Nivolumab + Daratumumab_Cohort B1
    Reporting group description
    		 ND regimen: Nivolumab (240 mg cycle 1, then 480 mg) + Daratumumab (16 mg/Kg)

    Reporting group title
    Nivolumab + Ipilimumab
    Reporting group description
    		 3 mg/kg of nivolumab and 1 mg/kg of ipilimumab Q3W for 4 doses, followed by nivolumab alone at 3 mg/kg Q2W

    Reporting group title
    Nivolumab + Daratumumab_Cohort A1
    Reporting group description
    		 ND regimen: Nivolumab (240 mg up to cycle 6, then 480 mg) + Daratumumab (16 mg/Kg)

    Serious adverse events
    		 Nivolumab Monotherapy (expansion) Nivolumab + Lirilumab Nivolumab + Daratumumab_Cohort B2 Nivolumab + Daratumumab_Cohort A2 Nivolumab + Daratumumab_Cohort B1 Nivolumab + Ipilimumab Nivolumab + Daratumumab_Cohort A1
    Total subjects affected by serious adverse events
         subjects affected / exposed
    50 / 105 (47.62%)
    34 / 72 (47.22%)
    9 / 22 (40.91%)
    5 / 5 (100.00%)
    15 / 41 (36.59%)
    39 / 65 (60.00%)
    3 / 6 (50.00%)
         number of deaths (all causes)
    53
    42
    13
    3
    24
    33
    1
         number of deaths resulting from adverse events
    16
    15
    5
    0
    4
    15
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant neoplasm progression
         subjects affected / exposed
    13 / 105 (12.38%)
    14 / 72 (19.44%)
    2 / 22 (9.09%)
    0 / 5 (0.00%)
    3 / 41 (7.32%)
    13 / 65 (20.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 15
    0 / 2
    0 / 0
    0 / 3
    0 / 13
    0 / 1
         deaths causally related to treatment / all
    0 / 12
    0 / 13
    0 / 2
    0 / 0
    0 / 2
    0 / 13
    0 / 0
    Neoplasm malignant
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    2 / 41 (4.88%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Second primary malignancy
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to skin
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tumour flare
         subjects affected / exposed
    0 / 105 (0.00%)
    2 / 72 (2.78%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tumour invasion
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myelodysplastic syndrome with single lineage dysplasia
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    2 / 105 (1.90%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    6 / 105 (5.71%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    7 / 65 (10.77%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 1
    0 / 0
    0 / 0
    1 / 1
    4 / 8
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    3 / 105 (2.86%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza like illness
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Graft versus host disease
         subjects affected / exposed
    2 / 105 (1.90%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    3 / 105 (2.86%)
    2 / 72 (2.78%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    5 / 65 (7.69%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    1 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pneumonitis
         subjects affected / exposed
    5 / 105 (4.76%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    4 / 65 (6.15%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    5 / 5
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    4 / 4
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute respiratory distress syndrome
         subjects affected / exposed
    2 / 105 (1.90%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atelectasis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Cough
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 105 (0.95%)
    2 / 72 (2.78%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Completed suicide
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    2 / 105 (1.90%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Product issues
    Stent malfunction
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Platelet count decreased
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver function test increased
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural fever
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural pneumothorax
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transfusion reaction
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Sinus tachycardia
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Ischaemic stroke
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ataxia
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cognitive disorder
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 105 (0.00%)
    2 / 72 (2.78%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Somnolence
         subjects affected / exposed
    2 / 105 (1.90%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myasthenic syndrome
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eosinophilia
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    3 / 105 (2.86%)
    4 / 72 (5.56%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    3 / 65 (4.62%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 4
    0 / 0
    0 / 0
    0 / 0
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperviscosity syndrome
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenitis
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombotic microangiopathy
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Diplopia
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vision blurred
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diverticular perforation
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune-mediated enterocolitis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal distension
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal mass
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Autoimmune pancreatitis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    3 / 65 (4.62%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 105 (0.00%)
    3 / 72 (4.17%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fistula of small intestine
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric perforation
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Autoimmune hepatitis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Hepatobiliary disease
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermatitis bullous
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pruritus
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermatitis psoriasiform
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash morbilliform
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    3 / 105 (2.86%)
    3 / 72 (4.17%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    3 / 65 (4.62%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Groin pain
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myositis
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    3 / 41 (7.32%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Pneumonia haemophilus
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 105 (2.86%)
    2 / 72 (2.78%)
    3 / 22 (13.64%)
    2 / 5 (40.00%)
    1 / 41 (2.44%)
    5 / 65 (7.69%)
    2 / 6 (33.33%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    1 / 3
    1 / 2
    0 / 3
    0 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    2 / 105 (1.90%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular device infection
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    4 / 65 (6.15%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalitis
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes simplex pharyngitis
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mucosal infection
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural infection
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Oral candidiasis
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia legionella
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    4 / 105 (3.81%)
    2 / 72 (2.78%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis syndrome
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia mycoplasmal
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Streptococcal infection
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Streptococcal bacteraemia
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypercalcaemia
         subjects affected / exposed
    3 / 105 (2.86%)
    3 / 72 (4.17%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    3 / 65 (4.62%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 105 (0.95%)
    2 / 72 (2.78%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    2 / 105 (1.90%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypervolaemia
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tumour lysis syndrome
         subjects affected / exposed
    0 / 105 (0.00%)
    2 / 72 (2.78%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Nivolumab Monotherapy (expansion) Nivolumab + Lirilumab Nivolumab + Daratumumab_Cohort B2 Nivolumab + Daratumumab_Cohort A2 Nivolumab + Daratumumab_Cohort B1 Nivolumab + Ipilimumab Nivolumab + Daratumumab_Cohort A1
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    102 / 105 (97.14%)
    69 / 72 (95.83%)
    16 / 22 (72.73%)
    5 / 5 (100.00%)
    35 / 41 (85.37%)
    62 / 65 (95.38%)
    6 / 6 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colorectal adenoma
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Tumour flare
         subjects affected / exposed
    0 / 105 (0.00%)
    4 / 72 (5.56%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences all number
    0
    4
    0
    0
    0
    1
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    6 / 105 (5.71%)
    1 / 72 (1.39%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    3 / 41 (7.32%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences all number
    9
    1
    1
    0
    3
    2
    0
    Hypotension
         subjects affected / exposed
    8 / 105 (7.62%)
    3 / 72 (4.17%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences all number
    10
    3
    0
    1
    0
    1
    0
    Hot flush
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    5 / 65 (7.69%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    1
    0
    0
    5
    2
    Flushing
         subjects affected / exposed
    3 / 105 (2.86%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    3
    0
    0
    1
    1
    0
    0
    Haematoma
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    1
    Varicose vein
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    3 / 105 (2.86%)
    3 / 72 (4.17%)
    1 / 22 (4.55%)
    1 / 5 (20.00%)
    4 / 41 (9.76%)
    3 / 65 (4.62%)
    0 / 6 (0.00%)
         occurrences all number
    4
    3
    1
    1
    4
    3
    0
    Chills
         subjects affected / exposed
    10 / 105 (9.52%)
    6 / 72 (8.33%)
    2 / 22 (9.09%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    10 / 65 (15.38%)
    0 / 6 (0.00%)
         occurrences all number
    11
    7
    3
    1
    0
    13
    0
    Fatigue
         subjects affected / exposed
    46 / 105 (43.81%)
    30 / 72 (41.67%)
    3 / 22 (13.64%)
    2 / 5 (40.00%)
    8 / 41 (19.51%)
    30 / 65 (46.15%)
    2 / 6 (33.33%)
         occurrences all number
    55
    34
    3
    2
    9
    30
    3
    Influenza like illness
         subjects affected / exposed
    0 / 105 (0.00%)
    4 / 72 (5.56%)
    2 / 22 (9.09%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences all number
    0
    6
    3
    0
    1
    1
    0
    Oedema peripheral
         subjects affected / exposed
    11 / 105 (10.48%)
    7 / 72 (9.72%)
    1 / 22 (4.55%)
    2 / 5 (40.00%)
    1 / 41 (2.44%)
    8 / 65 (12.31%)
    1 / 6 (16.67%)
         occurrences all number
    11
    7
    1
    4
    1
    8
    2
    Pain
         subjects affected / exposed
    5 / 105 (4.76%)
    3 / 72 (4.17%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    3 / 41 (7.32%)
    4 / 65 (6.15%)
    0 / 6 (0.00%)
         occurrences all number
    5
    3
    0
    0
    3
    4
    0
    Pyrexia
         subjects affected / exposed
    27 / 105 (25.71%)
    8 / 72 (11.11%)
    3 / 22 (13.64%)
    1 / 5 (20.00%)
    4 / 41 (9.76%)
    25 / 65 (38.46%)
    1 / 6 (16.67%)
         occurrences all number
    33
    9
    3
    1
    5
    34
    1
    Non-cardiac chest pain
         subjects affected / exposed
    3 / 105 (2.86%)
    4 / 72 (5.56%)
    2 / 22 (9.09%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    4 / 65 (6.15%)
    0 / 6 (0.00%)
         occurrences all number
    3
    4
    2
    0
    0
    4
    0
    Chest discomfort
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Feeling hot
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Peripheral swelling
         subjects affected / exposed
    3 / 105 (2.86%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    3
    0
    0
    1
    0
    0
    0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    1 / 22 (4.55%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Rhinitis allergic
         subjects affected / exposed
    2 / 105 (1.90%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    2 / 5 (40.00%)
    2 / 41 (4.88%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    1
    0
    2
    2
    0
    0
    Cough
         subjects affected / exposed
    29 / 105 (27.62%)
    11 / 72 (15.28%)
    0 / 22 (0.00%)
    2 / 5 (40.00%)
    4 / 41 (9.76%)
    22 / 65 (33.85%)
    3 / 6 (50.00%)
         occurrences all number
    45
    14
    0
    6
    4
    34
    3
    Dyspnoea
         subjects affected / exposed
    17 / 105 (16.19%)
    7 / 72 (9.72%)
    1 / 22 (4.55%)
    3 / 5 (60.00%)
    5 / 41 (12.20%)
    11 / 65 (16.92%)
    2 / 6 (33.33%)
         occurrences all number
    18
    7
    1
    4
    5
    15
    3
    Nasal congestion
         subjects affected / exposed
    11 / 105 (10.48%)
    4 / 72 (5.56%)
    0 / 22 (0.00%)
    2 / 5 (40.00%)
    1 / 41 (2.44%)
    14 / 65 (21.54%)
    2 / 6 (33.33%)
         occurrences all number
    15
    5
    0
    2
    1
    21
    2
    Rhinorrhoea
         subjects affected / exposed
    5 / 105 (4.76%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences all number
    6
    1
    0
    1
    0
    3
    0
    Bronchospasm
         subjects affected / exposed
    2 / 105 (1.90%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    3
    0
    0
    0
    0
    0
    1
    Dysphonia
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    2 / 65 (3.08%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    1
    Productive cough
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    1 / 22 (4.55%)
    2 / 5 (40.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    2
    0
    0
    0
    Tachypnoea
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    Upper-airway cough syndrome
         subjects affected / exposed
    5 / 105 (4.76%)
    0 / 72 (0.00%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    1 / 6 (16.67%)
         occurrences all number
    7
    0
    1
    0
    0
    1
    1
    Pleural effusion
         subjects affected / exposed
    5 / 105 (4.76%)
    3 / 72 (4.17%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    5 / 65 (7.69%)
    0 / 6 (0.00%)
         occurrences all number
    5
    3
    0
    0
    0
    5
    0
    Dyspnoea exertional
         subjects affected / exposed
    7 / 105 (6.67%)
    2 / 72 (2.78%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences all number
    7
    2
    1
    0
    1
    2
    0
    Oropharyngeal pain
         subjects affected / exposed
    2 / 105 (1.90%)
    3 / 72 (4.17%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    5 / 65 (7.69%)
    0 / 6 (0.00%)
         occurrences all number
    2
    3
    1
    0
    1
    5
    0
    Pneumonitis
         subjects affected / exposed
    9 / 105 (8.57%)
    2 / 72 (2.78%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    6 / 65 (9.23%)
    0 / 6 (0.00%)
         occurrences all number
    10
    5
    0
    0
    1
    8
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    7 / 105 (6.67%)
    5 / 72 (6.94%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    3 / 41 (7.32%)
    10 / 65 (15.38%)
    1 / 6 (16.67%)
         occurrences all number
    8
    5
    0
    0
    3
    10
    1
    Anxiety
         subjects affected / exposed
    6 / 105 (5.71%)
    5 / 72 (6.94%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    2 / 41 (4.88%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences all number
    6
    5
    0
    0
    2
    2
    0
    Investigations
    Neutrophil count decreased
         subjects affected / exposed
    1 / 105 (0.95%)
    6 / 72 (8.33%)
    0 / 22 (0.00%)
    3 / 5 (60.00%)
    2 / 41 (4.88%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences all number
    1
    7
    0
    9
    2
    2
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    4 / 105 (3.81%)
    6 / 72 (8.33%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    3 / 41 (7.32%)
    7 / 65 (10.77%)
    1 / 6 (16.67%)
         occurrences all number
    5
    7
    0
    0
    3
    10
    1
    Blood bilirubin increased
         subjects affected / exposed
    2 / 105 (1.90%)
    3 / 72 (4.17%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    4 / 65 (6.15%)
    0 / 6 (0.00%)
         occurrences all number
    2
    3
    0
    1
    0
    6
    0
    Blood creatinine increased
         subjects affected / exposed
    10 / 105 (9.52%)
    4 / 72 (5.56%)
    3 / 22 (13.64%)
    0 / 5 (0.00%)
    2 / 41 (4.88%)
    3 / 65 (4.62%)
    1 / 6 (16.67%)
         occurrences all number
    12
    4
    3
    0
    2
    9
    1
    Lipase increased
         subjects affected / exposed
    9 / 105 (8.57%)
    3 / 72 (4.17%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    1 / 41 (2.44%)
    8 / 65 (12.31%)
    1 / 6 (16.67%)
         occurrences all number
    10
    4
    0
    2
    2
    13
    1
    Amylase increased
         subjects affected / exposed
    1 / 105 (0.95%)
    4 / 72 (5.56%)
    0 / 22 (0.00%)
    2 / 5 (40.00%)
    0 / 41 (0.00%)
    5 / 65 (7.69%)
    0 / 6 (0.00%)
         occurrences all number
    1
    15
    0
    4
    0
    10
    0
    Platelet count decreased
         subjects affected / exposed
    0 / 105 (0.00%)
    7 / 72 (9.72%)
    1 / 22 (4.55%)
    2 / 5 (40.00%)
    0 / 41 (0.00%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences all number
    0
    8
    2
    3
    0
    2
    0
    White blood cell count decreased
         subjects affected / exposed
    4 / 105 (3.81%)
    8 / 72 (11.11%)
    1 / 22 (4.55%)
    2 / 5 (40.00%)
    0 / 41 (0.00%)
    4 / 65 (6.15%)
    0 / 6 (0.00%)
         occurrences all number
    4
    8
    1
    2
    0
    6
    0
    Bilirubin conjugated increased
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    0 / 105 (0.00%)
    2 / 72 (2.78%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    1 / 6 (16.67%)
         occurrences all number
    0
    8
    0
    0
    0
    1
    1
    Influenza A virus test positive
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    1
    Weight decreased
         subjects affected / exposed
    6 / 105 (5.71%)
    2 / 72 (2.78%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    4 / 65 (6.15%)
    0 / 6 (0.00%)
         occurrences all number
    6
    2
    0
    0
    1
    4
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    11 / 105 (10.48%)
    8 / 72 (11.11%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    9 / 65 (13.85%)
    0 / 6 (0.00%)
         occurrences all number
    12
    9
    0
    0
    1
    14
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    13 / 105 (12.38%)
    5 / 72 (6.94%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    8 / 65 (12.31%)
    0 / 6 (0.00%)
         occurrences all number
    15
    6
    0
    0
    1
    17
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    2 / 105 (1.90%)
    9 / 72 (12.50%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    6 / 65 (9.23%)
    0 / 6 (0.00%)
         occurrences all number
    2
    15
    0
    0
    0
    6
    0
    Lymphocyte count decreased
         subjects affected / exposed
    2 / 105 (1.90%)
    9 / 72 (12.50%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    6 / 65 (9.23%)
    0 / 6 (0.00%)
         occurrences all number
    2
    9
    4
    0
    2
    6
    0
    Weight increased
         subjects affected / exposed
    4 / 105 (3.81%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    7 / 65 (10.77%)
    0 / 6 (0.00%)
         occurrences all number
    4
    1
    0
    0
    0
    7
    0
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    4 / 105 (3.81%)
    13 / 72 (18.06%)
    4 / 22 (18.18%)
    2 / 5 (40.00%)
    10 / 41 (24.39%)
    10 / 65 (15.38%)
    2 / 6 (33.33%)
         occurrences all number
    6
    15
    4
    2
    10
    11
    2
    Fall
         subjects affected / exposed
    2 / 105 (1.90%)
    1 / 72 (1.39%)
    1 / 22 (4.55%)
    1 / 5 (20.00%)
    3 / 41 (7.32%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences all number
    2
    2
    1
    1
    7
    2
    0
    Foot fracture
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Fracture
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Hip fracture
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    Contusion
         subjects affected / exposed
    2 / 105 (1.90%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    3 / 65 (4.62%)
    1 / 6 (16.67%)
         occurrences all number
    2
    0
    0
    0
    1
    3
    1
    Skin laceration
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    7 / 65 (10.77%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    9
    0
    Sinus tachycardia
         subjects affected / exposed
    2 / 105 (1.90%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    3
    1
    0
    1
    1
    0
    0
    Angina pectoris
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    9 / 105 (8.57%)
    2 / 72 (2.78%)
    0 / 22 (0.00%)
    2 / 5 (40.00%)
    3 / 41 (7.32%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences all number
    9
    2
    0
    3
    3
    2
    0
    Headache
         subjects affected / exposed
    16 / 105 (15.24%)
    5 / 72 (6.94%)
    1 / 22 (4.55%)
    3 / 5 (60.00%)
    3 / 41 (7.32%)
    7 / 65 (10.77%)
    0 / 6 (0.00%)
         occurrences all number
    16
    6
    1
    3
    3
    8
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    3 / 105 (2.86%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    3 / 41 (7.32%)
    3 / 65 (4.62%)
    1 / 6 (16.67%)
         occurrences all number
    3
    1
    0
    1
    3
    4
    1
    Dysgeusia
         subjects affected / exposed
    2 / 105 (1.90%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    1 / 41 (2.44%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    2
    1
    1
    0
    Akathisia
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Lethargy
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    1
    Memory impairment
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    Paraesthesia
         subjects affected / exposed
    0 / 105 (0.00%)
    2 / 72 (2.78%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    1 / 65 (1.54%)
    1 / 6 (16.67%)
         occurrences all number
    0
    2
    0
    0
    1
    1
    2
    Syncope
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    1
    1
    0
    0
    Disturbance in attention
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    Neuropathy peripheral
         subjects affected / exposed
    9 / 105 (8.57%)
    1 / 72 (1.39%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences all number
    9
    1
    1
    0
    1
    2
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    23 / 105 (21.90%)
    18 / 72 (25.00%)
    4 / 22 (18.18%)
    4 / 5 (80.00%)
    10 / 41 (24.39%)
    12 / 65 (18.46%)
    3 / 6 (50.00%)
         occurrences all number
    26
    19
    6
    4
    13
    17
    3
    Neutropenia
         subjects affected / exposed
    12 / 105 (11.43%)
    7 / 72 (9.72%)
    2 / 22 (9.09%)
    4 / 5 (80.00%)
    9 / 41 (21.95%)
    6 / 65 (9.23%)
    1 / 6 (16.67%)
         occurrences all number
    15
    7
    2
    11
    15
    6
    1
    Thrombocytopenia
         subjects affected / exposed
    21 / 105 (20.00%)
    5 / 72 (6.94%)
    2 / 22 (9.09%)
    1 / 5 (20.00%)
    5 / 41 (12.20%)
    7 / 65 (10.77%)
    1 / 6 (16.67%)
         occurrences all number
    24
    6
    2
    1
    11
    13
    1
    Pancytopenia
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    0
    Leukopenia
         subjects affected / exposed
    13 / 105 (12.38%)
    4 / 72 (5.56%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences all number
    16
    5
    2
    0
    0
    1
    0
    Lymphopenia
         subjects affected / exposed
    9 / 105 (8.57%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences all number
    9
    2
    0
    0
    2
    2
    0
    Ear and labyrinth disorders
    Hypoacusis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Eye disorders
    Vision blurred
         subjects affected / exposed
    1 / 105 (0.95%)
    4 / 72 (5.56%)
    0 / 22 (0.00%)
    2 / 5 (40.00%)
    0 / 41 (0.00%)
    4 / 65 (6.15%)
    0 / 6 (0.00%)
         occurrences all number
    1
    5
    0
    2
    0
    4
    0
    Dry eye
         subjects affected / exposed
    1 / 105 (0.95%)
    2 / 72 (2.78%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    2 / 65 (3.08%)
    1 / 6 (16.67%)
         occurrences all number
    1
    2
    0
    0
    0
    2
    1
    Uveitis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    Vitreous haemorrhage
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    24 / 105 (22.86%)
    15 / 72 (20.83%)
    2 / 22 (9.09%)
    2 / 5 (40.00%)
    4 / 41 (9.76%)
    17 / 65 (26.15%)
    1 / 6 (16.67%)
         occurrences all number
    31
    17
    2
    2
    5
    22
    1
    Abdominal pain
         subjects affected / exposed
    9 / 105 (8.57%)
    5 / 72 (6.94%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    10 / 65 (15.38%)
    0 / 6 (0.00%)
         occurrences all number
    9
    8
    0
    1
    0
    13
    0
    Constipation
         subjects affected / exposed
    12 / 105 (11.43%)
    15 / 72 (20.83%)
    0 / 22 (0.00%)
    3 / 5 (60.00%)
    1 / 41 (2.44%)
    10 / 65 (15.38%)
    0 / 6 (0.00%)
         occurrences all number
    15
    16
    0
    3
    1
    10
    0
    Diarrhoea
         subjects affected / exposed
    28 / 105 (26.67%)
    21 / 72 (29.17%)
    4 / 22 (18.18%)
    4 / 5 (80.00%)
    6 / 41 (14.63%)
    20 / 65 (30.77%)
    1 / 6 (16.67%)
         occurrences all number
    38
    29
    4
    8
    11
    24
    1
    Vomiting
         subjects affected / exposed
    13 / 105 (12.38%)
    8 / 72 (11.11%)
    0 / 22 (0.00%)
    2 / 5 (40.00%)
    2 / 41 (4.88%)
    9 / 65 (13.85%)
    1 / 6 (16.67%)
         occurrences all number
    16
    8
    0
    2
    2
    12
    1
    Gastritis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    3 / 105 (2.86%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    2 / 5 (40.00%)
    1 / 41 (2.44%)
    3 / 65 (4.62%)
    0 / 6 (0.00%)
         occurrences all number
    3
    0
    0
    2
    1
    3
    0
    Large intestine polyp
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Abdominal hernia
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Abdominal distension
         subjects affected / exposed
    2 / 105 (1.90%)
    2 / 72 (2.78%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    4 / 65 (6.15%)
    0 / 6 (0.00%)
         occurrences all number
    2
    2
    0
    0
    0
    4
    0
    Dyspepsia
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    4 / 65 (6.15%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    4
    0
    Dry mouth
         subjects affected / exposed
    3 / 105 (2.86%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    4 / 65 (6.15%)
    0 / 6 (0.00%)
         occurrences all number
    3
    1
    0
    0
    1
    4
    0
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    8 / 105 (7.62%)
    2 / 72 (2.78%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    2 / 41 (4.88%)
    3 / 65 (4.62%)
    1 / 6 (16.67%)
         occurrences all number
    8
    2
    0
    0
    2
    3
    1
    Hyperhidrosis
         subjects affected / exposed
    6 / 105 (5.71%)
    2 / 72 (2.78%)
    1 / 22 (4.55%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences all number
    8
    4
    1
    1
    0
    2
    0
    Pruritus
         subjects affected / exposed
    25 / 105 (23.81%)
    9 / 72 (12.50%)
    0 / 22 (0.00%)
    4 / 5 (80.00%)
    4 / 41 (9.76%)
    11 / 65 (16.92%)
    1 / 6 (16.67%)
         occurrences all number
    29
    12
    0
    4
    4
    11
    1
    Rash
         subjects affected / exposed
    22 / 105 (20.95%)
    8 / 72 (11.11%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    1 / 41 (2.44%)
    12 / 65 (18.46%)
    0 / 6 (0.00%)
         occurrences all number
    26
    8
    0
    2
    1
    14
    0
    Rash maculo-papular
         subjects affected / exposed
    3 / 105 (2.86%)
    5 / 72 (6.94%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    3 / 41 (7.32%)
    8 / 65 (12.31%)
    0 / 6 (0.00%)
         occurrences all number
    3
    7
    1
    0
    3
    8
    0
    Erythema
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    1 / 22 (4.55%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    2
    0
    Night sweats
         subjects affected / exposed
    4 / 105 (3.81%)
    4 / 72 (5.56%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    4 / 65 (6.15%)
    0 / 6 (0.00%)
         occurrences all number
    4
    5
    0
    0
    0
    4
    0
    Alopecia
         subjects affected / exposed
    6 / 105 (5.71%)
    4 / 72 (5.56%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences all number
    6
    4
    0
    0
    1
    1
    0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    5 / 105 (4.76%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    3 / 65 (4.62%)
    0 / 6 (0.00%)
         occurrences all number
    5
    1
    0
    2
    0
    3
    0
    Proteinuria
         subjects affected / exposed
    3 / 105 (2.86%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    3
    0
    0
    1
    0
    0
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    6 / 105 (5.71%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    10 / 65 (15.38%)
    1 / 6 (16.67%)
         occurrences all number
    6
    1
    0
    0
    1
    10
    1
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    6 / 105 (5.71%)
    5 / 72 (6.94%)
    2 / 22 (9.09%)
    2 / 5 (40.00%)
    1 / 41 (2.44%)
    3 / 65 (4.62%)
    1 / 6 (16.67%)
         occurrences all number
    7
    5
    2
    2
    1
    3
    1
    Back pain
         subjects affected / exposed
    17 / 105 (16.19%)
    14 / 72 (19.44%)
    1 / 22 (4.55%)
    1 / 5 (20.00%)
    4 / 41 (9.76%)
    11 / 65 (16.92%)
    0 / 6 (0.00%)
         occurrences all number
    18
    14
    1
    1
    4
    13
    0
    Bone pain
         subjects affected / exposed
    2 / 105 (1.90%)
    1 / 72 (1.39%)
    2 / 22 (9.09%)
    1 / 5 (20.00%)
    6 / 41 (14.63%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences all number
    2
    1
    3
    1
    6
    2
    0
    Muscle spasms
         subjects affected / exposed
    8 / 105 (7.62%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    1 / 41 (2.44%)
    3 / 65 (4.62%)
    2 / 6 (33.33%)
         occurrences all number
    9
    0
    0
    1
    1
    4
    2
    Musculoskeletal chest pain
         subjects affected / exposed
    6 / 105 (5.71%)
    3 / 72 (4.17%)
    0 / 22 (0.00%)
    2 / 5 (40.00%)
    1 / 41 (2.44%)
    4 / 65 (6.15%)
    1 / 6 (16.67%)
         occurrences all number
    7
    3
    0
    2
    1
    4
    1
    Arthralgia
         subjects affected / exposed
    18 / 105 (17.14%)
    11 / 72 (15.28%)
    0 / 22 (0.00%)
    3 / 5 (60.00%)
    4 / 41 (9.76%)
    10 / 65 (15.38%)
    3 / 6 (50.00%)
         occurrences all number
    19
    13
    0
    4
    7
    12
    4
    Pain in extremity
         subjects affected / exposed
    9 / 105 (8.57%)
    6 / 72 (8.33%)
    1 / 22 (4.55%)
    1 / 5 (20.00%)
    3 / 41 (7.32%)
    5 / 65 (7.69%)
    1 / 6 (16.67%)
         occurrences all number
    11
    7
    1
    1
    3
    5
    1
    Arthritis
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    1 / 41 (2.44%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    1
    1
    1
    0
    Muscular weakness
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    2 / 65 (3.08%)
    1 / 6 (16.67%)
         occurrences all number
    1
    1
    0
    0
    1
    2
    1
    Neck pain
         subjects affected / exposed
    5 / 105 (4.76%)
    3 / 72 (4.17%)
    1 / 22 (4.55%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    3 / 65 (4.62%)
    1 / 6 (16.67%)
         occurrences all number
    5
    3
    1
    1
    0
    4
    1
    Sacral pain
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    6 / 105 (5.71%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    3 / 5 (60.00%)
    3 / 41 (7.32%)
    4 / 65 (6.15%)
    0 / 6 (0.00%)
         occurrences all number
    8
    1
    0
    3
    3
    5
    0
    Bronchitis
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 72 (1.39%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    5 / 41 (12.20%)
    1 / 65 (1.54%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    1
    0
    7
    1
    1
    Sinusitis
         subjects affected / exposed
    6 / 105 (5.71%)
    1 / 72 (1.39%)
    1 / 22 (4.55%)
    1 / 5 (20.00%)
    2 / 41 (4.88%)
    4 / 65 (6.15%)
    1 / 6 (16.67%)
         occurrences all number
    7
    1
    1
    1
    2
    6
    1
    Upper respiratory tract infection
         subjects affected / exposed
    17 / 105 (16.19%)
    13 / 72 (18.06%)
    3 / 22 (13.64%)
    4 / 5 (80.00%)
    9 / 41 (21.95%)
    10 / 65 (15.38%)
    2 / 6 (33.33%)
         occurrences all number
    21
    17
    4
    13
    12
    11
    4
    Urinary tract infection
         subjects affected / exposed
    7 / 105 (6.67%)
    3 / 72 (4.17%)
    2 / 22 (9.09%)
    0 / 5 (0.00%)
    2 / 41 (4.88%)
    4 / 65 (6.15%)
    0 / 6 (0.00%)
         occurrences all number
    17
    3
    2
    0
    2
    4
    0
    Bronchitis haemophilus
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Cellulitis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    2 / 65 (3.08%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    2
    0
    Oral candidiasis
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 72 (1.39%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    0
    1
    0
    1
    0
    Paronychia
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Pneumonia haemophilus
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    2 / 22 (9.09%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    COVID-19
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    1 / 22 (4.55%)
    1 / 5 (20.00%)
    1 / 41 (2.44%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    0
    Wound infection
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    17 / 105 (16.19%)
    14 / 72 (19.44%)
    3 / 22 (13.64%)
    1 / 5 (20.00%)
    2 / 41 (4.88%)
    12 / 65 (18.46%)
    0 / 6 (0.00%)
         occurrences all number
    18
    14
    3
    2
    2
    12
    0
    Hyperuricaemia
         subjects affected / exposed
    12 / 105 (11.43%)
    2 / 72 (2.78%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    3 / 65 (4.62%)
    1 / 6 (16.67%)
         occurrences all number
    13
    2
    0
    0
    0
    4
    1
    Hypercalcaemia
         subjects affected / exposed
    9 / 105 (8.57%)
    4 / 72 (5.56%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    4 / 65 (6.15%)
    1 / 6 (16.67%)
         occurrences all number
    10
    4
    0
    0
    0
    4
    1
    Hyperglycaemia
         subjects affected / exposed
    16 / 105 (15.24%)
    8 / 72 (11.11%)
    2 / 22 (9.09%)
    2 / 5 (40.00%)
    0 / 41 (0.00%)
    11 / 65 (16.92%)
    1 / 6 (16.67%)
         occurrences all number
    17
    9
    2
    3
    0
    17
    2
    Hyperkalaemia
         subjects affected / exposed
    2 / 105 (1.90%)
    3 / 72 (4.17%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    4 / 65 (6.15%)
    0 / 6 (0.00%)
         occurrences all number
    2
    3
    0
    1
    0
    4
    0
    Dehydration
         subjects affected / exposed
    3 / 105 (2.86%)
    2 / 72 (2.78%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    6 / 65 (9.23%)
    0 / 6 (0.00%)
         occurrences all number
    4
    3
    0
    1
    0
    6
    0
    Hypocalcaemia
         subjects affected / exposed
    14 / 105 (13.33%)
    5 / 72 (6.94%)
    3 / 22 (13.64%)
    0 / 5 (0.00%)
    1 / 41 (2.44%)
    7 / 65 (10.77%)
    1 / 6 (16.67%)
         occurrences all number
    16
    6
    4
    0
    1
    10
    1
    Hypokalaemia
         subjects affected / exposed
    11 / 105 (10.48%)
    1 / 72 (1.39%)
    2 / 22 (9.09%)
    1 / 5 (20.00%)
    3 / 41 (7.32%)
    3 / 65 (4.62%)
    0 / 6 (0.00%)
         occurrences all number
    13
    1
    2
    1
    3
    5
    0
    Hypomagnesaemia
         subjects affected / exposed
    4 / 105 (3.81%)
    0 / 72 (0.00%)
    2 / 22 (9.09%)
    4 / 5 (80.00%)
    3 / 41 (7.32%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    5
    0
    3
    7
    5
    0
    0
    Hyponatraemia
         subjects affected / exposed
    9 / 105 (8.57%)
    7 / 72 (9.72%)
    1 / 22 (4.55%)
    1 / 5 (20.00%)
    2 / 41 (4.88%)
    5 / 65 (7.69%)
    0 / 6 (0.00%)
         occurrences all number
    9
    11
    1
    1
    3
    10
    0
    Hypophosphataemia
         subjects affected / exposed
    8 / 105 (7.62%)
    5 / 72 (6.94%)
    2 / 22 (9.09%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    5 / 65 (7.69%)
    0 / 6 (0.00%)
         occurrences all number
    9
    5
    2
    1
    0
    9
    0
    Hypermagnesaemia
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    0
    0
    0
    3
    2
    Hypoglycaemia
         subjects affected / exposed
    3 / 105 (2.86%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    1 / 65 (1.54%)
    1 / 6 (16.67%)
         occurrences all number
    3
    0
    0
    0
    0
    1
    1
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 22 (0.00%)
    1 / 5 (20.00%)
    0 / 41 (0.00%)
    0 / 65 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Hypoalbuminaemia
         subjects affected / exposed
    10 / 105 (9.52%)
    2 / 72 (2.78%)
    1 / 22 (4.55%)
    0 / 5 (0.00%)
    0 / 41 (0.00%)
    6 / 65 (9.23%)
    0 / 6 (0.00%)
         occurrences all number
    11
    2
    3
    0
    0
    6
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Dec 2012
    Eliminate the highest (10 mg/kg) of three dose levels scheduled to be examined, require that 8 of 16 subjects with multiple myeloma be required to undergo bone marrow biopsy while on therapy, and modify the discontinuation criteria to be more stringent
    25 Jun 2013
    Eliminate the CML cohort in the expansion phase as recruitment would be difficult due to lack of concomitant therapy with a tyrosine kinase inhibitor and increase the size of the remaining four cohorts from 16 to 23 subjects to redistribute the allotted patients from the eliminated CML cohort.
    19 Dec 2013
    Adds an additional set of cohorts (approximately 75 additional subjects) for dose escalation and dose expansion with combination of ipilimumab and nivolumab.
    20 Aug 2014
    Adds an additional set of cohorts (approximately 80 additional subjects) for dose expansion with combination of lirilumab and nivolumab
    05 Feb 2015
    Removes exploratory cohorts from the nivolumab/ipilimumab cohorts
    09 Aug 2016
    Adds an additional set of cohorts (approximately 60 additional subjects) for dose expansion in multiple myeloma patients treated with Nivolumab and Daratumumab with or without Pomalidomide and Dexamethasone
    19 Jan 2017
    This amendment includes corrections and updates pertinent only to the nivolumab/daratumumab cohorts. Additional biomarkers evaluations from peripheral blood specimens have been included. Daratumumab specific requirements for eligibility, dose delays and discontinuation, drug preparation and administration. Prevention and management of infusion related reactions, and permitted and restricted treatments have been aligned with the daratumumab IB and daratumumab standard protocol elements.
    04 Aug 2017
    Major changes are corrections and updates pertinent only to the nivolumab/daratumumab cohorts as follows:  Changes in eligibility for subjects with multiple myeloma (MM) for enrollment in the nivolumab/daratumumab cohorts include: − Eligible subjects must have failed prior treatment with an immune modulatory drug (IMiD) and/or a proteasome inhibitor (PI) rather than the requirement of failure to treatment with both prior treatment types. Refractory and relapsed refractory definitions removed as criterion definitions. − Subjects who received prior treatment with pomalidomide are no longer excluded from eligibility.  The randomization ratio has been changed to a 2:1 ratio, which increases the nivolumab + daratumumab + pomalidomide (NDPd) regimen cohort to 40 and reduces the nivolumab + daratumumab (ND) regimen cohort to 20. The sample size calculation has been updated to support change in randomization ratio.  Changes to the biomarkers plan were made to align with the program level approach and small corrections were made to the biomarkers collections schedule to ensure consistency throughout the protocol. In addition, Biomarker collections from peripheral blood specimens have been clarified to remove duplicate collections.  Daratumumab specific requirements for dose delays and discontinuation, drug preparation and administration, prevention and management of infusion related reactions, and permitted and restricted treatments have been aligned with the daratumumab IB and daratumumab standard protocol elements.
    15 Feb 2018
    Major changes:  In compliance with requests from the FDA, enrollment into the nivolumab +daratumumab with and without pomalidomide (NDPd: Cohort A) has been stopped. Cohort B (nivolumab +daratumumab vs daratumumab monotherapy [ND, D]) has been opened, with at 2:1 randomization. o Eligibility changes to the patient population for patients to be enrolled in Cohort B and toxicity stopping rules for the ND arm have been incorporated. o Cohort B patients (only) treated in the ND arm: Dose regimen change: nivolumab 480 mg every 4 weeks (Day 1) will begin at Cycle 2 rather than at Cycle 7 and continue until the end of treatment. Cycle 1 dose: 240 mg on Day 15.  The biomarker assessments have been aligned to the multiple myeloma program wide biomarkers evaluations.  All content related to the nivolumab +ipilimumab combination has been removed because all study procedures for this cohort, including follow-up evaluations, have been completed.
    23 Apr 2019
    Incorporated Administrative Letter 10  Updated the medical monitor  Removed all references to the lirilumab/nivolumab and nivolumab monotherapy cohorts.  Removed all references to the dose selection phase.  Removed references to non-Hodgkin and Hodgkin lymphoma.  Added option for split-dosing of daratumumab at C1D1  Added requirements for HBV DNA testing and updated requirements for hepatitis B and C criteria and testing to address daratumumab safety concerns  Clarified timing of interim and final analyses.  Deleted appendices that are no longer applicable

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

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

    European Medicines Agency © 1995-Thu Aug 21 12:32:37 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA