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    Clinical Trial Results:
    A Phase Ib/II, open label, multicenter study of MCS110 in combination with PDR001 in patients with advanced malignancies

    Summary
    EudraCT number
    		 2016-000210-29
    Trial protocol
    		 FI   DE   ES   FR   BE   IT  
    Global end of trial date
    04 Jun 2020

    Results information
    Results version number
    		 v2(current)
    This version publication date
    23 Aug 2021
    First version publication date
    12 Jun 2021
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CMCS110Z2102
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02807844
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    Novartis Campus, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.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
    04 Jun 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Jun 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Phase Ib part: To characterize the safety and tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Phase II part: To estimate the anti-tumor activity of the combination of MCS110 with PDR001
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 Jun 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Finland: 12
    Country: Number of subjects enrolled
    France: 5
    Country: Number of subjects enrolled
    Germany: 12
    Country: Number of subjects enrolled
    Hong Kong: 3
    Country: Number of subjects enrolled
    Italy: 15
    Country: Number of subjects enrolled
    Japan: 5
    Country: Number of subjects enrolled
    Korea, Republic of: 17
    Country: Number of subjects enrolled
    Spain: 40
    Country: Number of subjects enrolled
    Switzerland: 17
    Country: Number of subjects enrolled
    United States: 13
    Worldwide total number of subjects
    141
    EEA total number of subjects
    86
    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)
    95
    From 65 to 84 years
    46
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 In Phase Ib: planned minimum 15 patients; analyzed 60 patients. In Phase II: planned approximatively 20 patients in each group (80); analyzed 81 patients.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W
    Arm description
    		 Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W
    Arm type
    		 Experimental

    Investigational medicinal product name
    PDR001
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 mg Every 3 weeks

    Investigational medicinal product name
    MCS110
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1 mg/kg Every 3 weeks

    Arm title
    		 Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W
    Arm description
    		 Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W
    Arm type
    		 Experimental

    Investigational medicinal product name
    MCS110
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    3 mg/kg Every 3 weeks

    Investigational medicinal product name
    PDR001
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 mg Every 3 weeks

    Arm title
    		 Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W
    Arm description
    		 Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W
    Arm type
    		 Experimental

    Investigational medicinal product name
    MCS110
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    3 mg/kg Every 3 weeks

    Investigational medicinal product name
    PDR001
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg Every 3 weeks

    Arm title
    		 Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W
    Arm description
    		 Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W
    Arm type
    		 Experimental

    Investigational medicinal product name
    MCS110
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    5 mg/kg Every 3 weeks

    Investigational medicinal product name
    PDR001
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg Every 3 weeks

    Arm title
    		 Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W
    Arm description
    		 Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W
    Arm type
    		 Experimental

    Investigational medicinal product name
    PDR001
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg Every 3 weeks

    Investigational medicinal product name
    MCS110
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    7.5 mg/kg Every 3 weeks

    Arm title
    		 Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Arm description
    		 Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Arm type
    		 Experimental

    Investigational medicinal product name
    MCS110
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    10 mg/kg Every 3 weeks

    Investigational medicinal product name
    PDR001
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg Every 3 weeks

    Arm title
    		 Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC
    Arm description
    		 Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC)
    Arm type
    		 Experimental

    Investigational medicinal product name
    MCS110
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    7.5 mg/kg Every 3 weeks

    Investigational medicinal product name
    PDR001
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg Every 3 weeks

    Arm title
    		 Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC
    Arm description
    		 Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC)
    Arm type
    		 Experimental

    Investigational medicinal product name
    MCS110
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    7.5 mg/kg Every 3 weeks

    Investigational medicinal product name
    PDR001
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg Every 3 weeks

    Arm title
    		 Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC
    Arm description
    		 Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC)
    Arm type
    		 Experimental

    Investigational medicinal product name
    MCS110
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    7.5 mg/kg Every 3 weeks

    Investigational medicinal product name
    PDR001
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg Every 3 weeks

    Arm title
    		 Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm description
    		 Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Arm type
    		 Experimental

    Investigational medicinal product name
    MCS110
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    7.5 mg/kg Every 3 weeks

    Investigational medicinal product name
    PDR001
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg Every 3 weeks

    Number of subjects in period 1
    		Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Started
    6
    12
    12
    13
    6
    11
    20
    20
    21
    20
    Completed
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Not completed
    6
    12
    12
    13
    6
    11
    20
    20
    21
    20
         Adverse event, serious fatal
    -
    -
    2
    4
    1
    2
    1
    2
    -
    1
         Consent withdrawn by subject
    -
    -
    2
    1
    1
    -
    1
    -
    -
    -
         Physician decision
    -
    -
    -
    -
    -
    -
    3
    -
    1
    2
         Adverse event, non-fatal
    1
    -
    -
    -
    1
    1
    1
    1
    1
    2
         Progressive disease
    5
    12
    8
    8
    3
    8
    14
    17
    19
    15

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W
    Reporting group description
    		 Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W

    Reporting group title
    Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W
    Reporting group description
    		 Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W

    Reporting group title
    Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W
    Reporting group description
    		 Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W

    Reporting group title
    Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W
    Reporting group description
    		 Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W

    Reporting group title
    Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W
    Reporting group description
    		 Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W

    Reporting group title
    Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Reporting group description
    		 Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W

    Reporting group title
    Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC
    Reporting group description
    		 Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC)

    Reporting group title
    Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC
    Reporting group description
    		 Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC)

    Reporting group title
    Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC
    Reporting group description
    		 Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC)

    Reporting group title
    Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Reporting group description
    		 Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)

    Reporting group values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME Total
    Number of subjects
    		 6 12 12 13 6 11 20 20 21 20 141
    Age Categorical
    Units: Participants
        <=18 years
    		 0 0 0 0 0 0 0 0 0 0 0
        Between 18 and 65 years
    		 3 9 8 10 5 8 20 11 9 12 95
        >=65 years
    		 3 3 4 3 1 3 0 9 12 8 46
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 64.3 ± 14.72 56.9 ± 11.13 59.3 ± 9.94 55.4 ± 10.03 57.3 ± 14.02 58.6 ± 11.13 50.0 ± 8.29 61.5 ± 11.33 62.8 ± 10.13 60.7 ± 13.15 -
    Sex: Female, Male
    Units: Participants
        Female
    		 4 10 6 8 4 6 20 8 21 9 96
        Male
    		 2 2 6 5 2 5 0 12 0 11 45
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0 0 0 0 0 0 0
        Asian
    		 0 0 1 2 1 2 5 4 4 7 26
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0 0 0 0 0 0 0
        Black or African American
    		 0 0 0 0 0 0 0 1 0 0 1
        White
    		 5 12 10 11 5 9 14 14 14 12 106
        More than one race
    		 0 0 0 0 0 0 0 0 1 0 1
        Unknown or Not Reported
    		 1 0 1 0 0 0 1 1 2 1 7

    End points

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    End points reporting groups
    Reporting group title
    Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W
    Reporting group description
    		 Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W

    Reporting group title
    Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W
    Reporting group description
    		 Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W

    Reporting group title
    Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W
    Reporting group description
    		 Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W

    Reporting group title
    Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W
    Reporting group description
    		 Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W

    Reporting group title
    Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W
    Reporting group description
    		 Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W

    Reporting group title
    Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Reporting group description
    		 Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W

    Reporting group title
    Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC
    Reporting group description
    		 Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC)

    Reporting group title
    Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC
    Reporting group description
    		 Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC)

    Reporting group title
    Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC
    Reporting group description
    		 Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC)

    Reporting group title
    Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Reporting group description
    		 Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)

    Primary: Phase Ib: Percentage of participants with adverse events, as a measure of safety

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    End point title
    		 Phase Ib: Percentage of participants with adverse events, as a measure of safety [1] [2]
    End point description
    Phase Ib: To characterize the safety and tolerability of MCS110 in combination with PDR001 in patients with advanced solid malignancies and to identify a recommended dose combination for Phase II.
    End point type
    Primary
    End point timeframe
    From start of treatment to a maximum timeframe of 116.4 weeks for phase Ib
    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: This endpoint only applied to phase Ib arms and not phase II arms.
    [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: This endpoint only applied to phase Ib arms and not phase II arms.
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Number of subjects analysed
    6
    12
    12
    13
    6
    11
    Units: Participants
        Adverse events (AEs) - all grades
    6
    12
    12
    13
    6
    11
        AEs - Treatment-related - all grades
    6
    12
    11
    8
    6
    8
        SAEs - all grades
    3
    4
    4
    7
    2
    5
        SAEs - Treatment-related - all grades
    0
    1
    0
    0
    2
    1
        Fatal SAEs - all grades
    0
    0
    0
    2
    0
    0
        Fatal SAEs - Treatt-related - all grades
    0
    0
    0
    0
    0
    0
        AEs leading to disc.- all grades
    0
    0
    0
    0
    2
    1
        AEs leading to disc.- Treat-related - all grades
    0
    0
    0
    0
    2
    1
        AEs leading to dose adjust / interrupt-all grades
    4
    4
    4
    2
    2
    6
        AEs requiring addit. therapy - all grades
    6
    12
    10
    12
    4
    10
    No statistical analyses for this end point

    Primary: Phase II : Overall Response rate (ORR) - per RECIST v1.1

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    End point title
    		 Phase II : Overall Response rate (ORR) - per RECIST v1.1 [3] [4]
    End point description
    Overall Response Rate (ORR) is defined as the proportion of patients with a best overall response assessed by CT scan or MRI of complete response (CR), disappearance of all measurable and non-measurable lesions or partial response (PR), at least a 30% decrease in the sum of diameter of all measurable lesions, taking as reference the baseline sum of diameters,. based on local Investigator assessment, as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1).
    End point type
    Primary
    End point timeframe
    4 years
    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: This endpoint only applied to phase II arms and not phase Ib arms.
    [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: This endpoint only applied to phase II arms and not phase Ib arms.
    End point values
    		 Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    20
    20
    21
    20
    Units: Percentage of participants
        number (confidence interval 90%)
    5 (0.3 to 21.6)
    0 (0.0 to 13.9)
    9.5 (1.7 to 27.1)
    0 (0.0 to 13.9)
    No statistical analyses for this end point

    Primary: Phase II : Bayesian inference of Overall Response rate (ORR) - per RECIST v1.1 - mean

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    End point title
    		 Phase II : Bayesian inference of Overall Response rate (ORR) - per RECIST v1.1 - mean [5] [6]
    End point description
    Overall Response Rate (ORR) is defined as the proportion of patients with a best overall response assessed by CT scan or MRI of complete response (CR), disappearance of all measurable and non-measurable lesions or partial response (PR), at least a 30% decrease in the sum of diameter of all measurable lesions, taking as reference the baseline sum of diameters,. based on local Investigator assessment, as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) - mean (FAS).
    End point type
    Primary
    End point timeframe
    4 years
    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: This endpoint only applied to phase II arms and not phase Ib arms.
    [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: This endpoint only applied to phase II arms and not phase Ib arms.
    End point values
    		 Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    20
    20
    21
    20
    Units: Percentage of participants
        arithmetic mean (confidence interval 90%)
    6.7 (0.8 to 17.1)
    999 (999 to 999)
    10.8 (2.6 to 23.1)
    0.8 (0 to 4.5)
    No statistical analyses for this end point

    Primary: Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) - per RECIST v1.1

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    End point title
    		 Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) - per RECIST v1.1 [7] [8]
    End point description
    Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per investigator based on Response evaluation criteria in solid tumors (RECIST) v1.1
    End point type
    Primary
    End point timeframe
    4 years
    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: This endpoint only applied to phase II arms and not phase Ib arms.
    [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: This endpoint only applied to phase II arms and not phase Ib arms.
    End point values
    		 Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    20
    20
    21
    20
    Units: Percentage of participants
        number (confidence interval 90%)
    20 (7.1 to 40.1)
    0 (0.0 to 13.9)
    9.5 (1.7 to 27.1)
    10.0 (1.8 to 28.3)
    No statistical analyses for this end point

    Primary: Phase II: Bayesian inference of Clinical Benefit Rate - per RECIST v1.1- mean

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    End point title
    		 Phase II: Bayesian inference of Clinical Benefit Rate - per RECIST v1.1- mean [9] [10]
    End point description
    Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per investigator based on Response evaluation criteria in solid tumors (RECIST) v1.1
    End point type
    Primary
    End point timeframe
    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: This endpoint only applied to phase II arms and not phase Ib arms.
    [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: This endpoint only applied to phase II arms and not phase Ib arms.
    End point values
    		 Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    20
    20
    21
    20
    Units: Percentage of participants
        arithmetic mean (confidence interval 90%)
    999 (999 to 999)
    0.8 (0 to 4.5)
    999 (999 to 999)
    999 (999 to 999)
    No statistical analyses for this end point

    Primary: Phase Ib: Planned Dose intensity - MCS110

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    End point title
    		 Phase Ib: Planned Dose intensity - MCS110 [11] [12]
    End point description
    To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Planned dose intensity for MCS110 is cumulative planned dose (mg/kg)/ number of doses scheduled per protocol during treatment period (i.e., this is equivalent to planned dose level).
    End point type
    Primary
    End point timeframe
    Measured up to a max of 112.4 weeks
    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: This endpoint only applied to phase Ib arms and not phase II arms.
    [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: This endpoint only applied to phase Ib arms and not phase II arms.
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Number of subjects analysed
    6
    12
    12
    13
    6
    11
    Units: mg/kg/3wks
        arithmetic mean (standard deviation)
    0.86 ± 0.191
    2.74 ± 0.386
    2.66 ± 0.435
    4.85 ± 0.286
    7.05 ± 0.594
    9.47 ± 1.093
    No statistical analyses for this end point

    Primary: Phase Ib: Relative Dose intensity - MCS110

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    End point title
    		 Phase Ib: Relative Dose intensity - MCS110 [13] [14]
    End point description
    To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Relative dose intensity (%) is 100 × dose intensity (mg/kg/3wks)/planned dose intensity (mg/kg/3wks).
    End point type
    Primary
    End point timeframe
    Measured up to a max of 112.4 weeks
    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: This endpoint only applied to phase Ib arms and not phase II arms.
    [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: This endpoint only applied to phase Ib arms and not phase II arms.
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Number of subjects analysed
    6
    12
    12
    13
    6
    11
    Units: Percentage
        arithmetic mean (standard deviation)
    100 ± 100
    100 ± 100
    100 ± 100
    99.23 ± 2.774
    100 ± 100
    100 ± 100
    No statistical analyses for this end point

    Primary: Phase Ib: Planned Dose intensity - PDR001

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    End point title
    		 Phase Ib: Planned Dose intensity - PDR001 [15] [16]
    End point description
    To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Planned dose intensity for PDR001 (mg/3wks) is planned cumulative dose (mg)/ number of doses scheduled per protocol during treatment period (i.e., this is equivalent to planned dose level).
    End point type
    Primary
    End point timeframe
    Measured up to a max of 112.4 weeks
    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: This endpoint only applied to phase Ib arms and not phase II arms.
    [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: This endpoint only applied to phase Ib arms and not phase II arms.
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Number of subjects analysed
    6
    12
    12
    13
    6
    11
    Units: mg/3wks
        arithmetic mean (standard deviation)
    86.09 ± 19.058
    91.18 ± 12.873
    265.83 ± 43.528
    293.59 ± 16.013
    282.12 ± 23.773
    289.04 ± 20.329
    No statistical analyses for this end point

    Primary: Phase Ib: Relative Dose intensity - PDR001

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    End point title
    		 Phase Ib: Relative Dose intensity - PDR001 [17] [18]
    End point description
    To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Relative dose intensity (%) is 100 × dose intensity (mg/3wks)/planned dose intensity (mg/3wks).
    End point type
    Primary
    End point timeframe
    Measured up to a max of 112.4 weeks
    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: This endpoint only applied to phase Ib arms and not phase II arms.
    [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: This endpoint only applied to phase Ib arms and not phase II arms.
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Number of subjects analysed
    6
    12
    12
    13
    6
    11
    Units: Percentage
        arithmetic mean (standard deviation)
    100.00 ± 100.00
    100.00 ± 100.00
    100.00 ± 100.00
    100.00 ± 100.00
    100.00 ± 100.00
    100.00 ± 100.00
    No statistical analyses for this end point

    Primary: Phase Ib: Number of Participants with Dose Reductions

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    End point title
    		 Phase Ib: Number of Participants with Dose Reductions [19] [20]
    End point description
    To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.
    End point type
    Primary
    End point timeframe
    Measured up to a max of 112.4 weeks
    Notes
    [19] - 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: This endpoint only applied to phase Ib arms and not phase II arms.
    [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: This endpoint only applied to phase Ib arms and not phase II arms.
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Number of subjects analysed
    6
    12
    12
    13
    6
    11
    Units: Participants
        n of participants with no dose reduction- MCS110
    6
    12
    12
    13
    6
    9
        n of participants with no dose reduction- PDR001
    6
    12
    12
    13
    6
    11
    No statistical analyses for this end point

    Primary: Phase Ib: Number of dose interruptions per participant

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    End point title
    		 Phase Ib: Number of dose interruptions per participant [21] [22]
    End point description
    To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.
    End point type
    Primary
    End point timeframe
    Measured up to a max of 112.4 weeks
    Notes
    [21] - 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: This endpoint only applied to phase Ib arms and not phase II arms.
    [22] - 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: This endpoint only applied to phase Ib arms and not phase II arms.
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Number of subjects analysed
    6
    12
    12
    13
    6
    11
    Units: Dose interruptions per participant
    arithmetic mean (standard deviation)
        Number of dose interruptions per subject - MCS110
    1.3 ± 1.97
    0.3 ± 0.45
    0.3 ± 0.45
    0.0 ± 0.0
    0.3 ± 0.52
    0.1 ± 0.30
        Number of dose interruptions per subject - PDR001
    1.3 ± 1.97
    0.3 ± 0.45
    0.3 ± 0.45
    0.0 ± 0.0
    0.3 ± 0.52
    0.1 ± 0.30
    No statistical analyses for this end point

    Primary: Phase Ib: Number of subjects with at least one dose interruption

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    End point title
    		 Phase Ib: Number of subjects with at least one dose interruption [23] [24]
    End point description
    To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.
    End point type
    Primary
    End point timeframe
    Measured up to a max of 112.4 weeks
    Notes
    [23] - 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: This endpoint only applied to phase Ib arms and not phase II arms.
    [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: This endpoint only applied to phase Ib arms and not phase II arms.
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Number of subjects analysed
    6
    12
    12
    13
    6
    11
    Units: Participants
        N w/ at least 1 dose interruption - MCS110
    3
    3
    3
    0
    2
    1
        N w/ at least 1 dose interruption - PDR001
    3
    3
    3
    0
    2
    1
    No statistical analyses for this end point

    Primary: Phase Ib: Number of Participants with Dose Limiting Toxicities (DLTs) During the First 2 Cycles of Study Treatment

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    End point title
    		 Phase Ib: Number of Participants with Dose Limiting Toxicities (DLTs) During the First 2 Cycles of Study Treatment [25] [26]
    End point description
    Phase Ib: Dose limiting toxicities occurring during the first 2 cycles by system organ class, preferred term and maximum grade for Phase Ib. The National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 4.03 was used for all grading. (CPK = Creatine Phosphokinase )
    End point type
    Primary
    End point timeframe
    the first 2 cycles of study treatment; cycle = 21 days (i.e., at day 42)
    Notes
    [25] - 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: This endpoint only applied to phase Ib arms and not phase II arms.
    [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: This endpoint only applied to phase Ib arms and not phase II arms.
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Number of subjects analysed
    5
    11
    9
    7
    4
    4
    Units: Participants
        n w/ at least 1 event - all grades(n=5,11,9,7,4,4)
    0
    0
    1
    0
    0
    1
        n Investigations - all grades (n=5,11,9,7,4,4)
    0
    0
    1
    0
    0
    1
        n Blood CPK increased (n=5,11,9,7,4,4)
    0
    0
    1
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Phase II : Overall Response rate (ORR) - per irRC

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    End point title
    		 Phase II : Overall Response rate (ORR) - per irRC [27]
    End point description
    Phase II: Overall Response Rate (Complete response (CR) or Partial response (PR)) (with confirmation) as per investigator based on immune related Response criteria (irRC) (FAS)
    End point type
    Secondary
    End point timeframe
    4 years
    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: This endpoint only applied to phase II arms and not phase Ib arms.
    End point values
    		 Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    20
    20
    21
    20
    Units: Percentage of participants
        number (confidence interval 90%)
    5 (0.3 to 21.6)
    0 (0.0 to 13.9)
    9.5 (1.7 to 27.1)
    0 (0.0 to 13.9)
    No statistical analyses for this end point

    Secondary: Phase Ib: Overall Response Rate (ORR)

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    End point title
    		 Phase Ib: Overall Response Rate (ORR) [28]
    End point description
    Phase Ib: Overall Response Rate (Complete response (CR) or Partial response (PR)), per RECIST v1.1 and per immune related Response criteria (irRC)
    End point type
    Secondary
    End point timeframe
    4 years
    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: This endpoint only applied to phase Ib arms and not phase II arms.
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Number of subjects analysed
    6
    12
    12
    13
    6
    11
    Units: Percentage of participants
    number (confidence interval 90%)
        Overall Response Rate - RECIST v1.1
    16.7 (0.9 to 58.2)
    0 (0.0 to 22.1)
    0 (0.0 to 22.1)
    0 (0.0 to 20.6)
    0 (0.0 to 39.3)
    9.1 (0.5 to 36.4)
        Overall Response Rate - irRC
    16.7 (0.9 to 58.2)
    0 (0.0 to 22.1)
    0 (0.0 to 22.1)
    0 (0.0 to 20.6)
    0 (0.0 to 39.3)
    9.1 (0.5 to 36.4)
    No statistical analyses for this end point

    Secondary: Phase II : Bayesian inference of Overall Response rate (ORR) - per irRC - mean

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    End point title
    		 Phase II : Bayesian inference of Overall Response rate (ORR) - per irRC - mean [29]
    End point description
    Full Analysis Set. Since objective responses are rare in advanced pancreatic cancer and that long lasting stable disease is considered beneficial to patients, clinical benefit rate (confirmed objective response or SD>4 months) was used as the primary endpoint for antitumor activity in this study changed from objective response to for this patient population.
    End point type
    Secondary
    End point timeframe
    4 years
    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: This endpoint only applied to phase II arms and not phase Ib arms.
    End point values
    		 Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    20
    0 [30]
    21
    20
    Units: Percentage of participants
        arithmetic mean (confidence interval 90%)
    6.7 (0.8 to 17.1)
    ( to )
    10.8 (2.6 to 23.1)
    0.8 (0 to 4.5)
    Notes
    [30] - See Bayesian inference of Clinical Benefit Rate - per irRC - mean results
    No statistical analyses for this end point

    Secondary: Phase 1b: Clinical Benefit Rate (CBR)

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    End point title
    		 Phase 1b: Clinical Benefit Rate (CBR) [31]
    End point description
    Phase 1b: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per RECIST v1.1 and per immune related Response criteria (irRC)
    End point type
    Secondary
    End point timeframe
    4 years
    Notes
    [31] - 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: This endpoint only applied to phase Ib arms and not phase II arms.
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Number of subjects analysed
    6
    12
    12
    13
    6
    11
    Units: Percentage of participants
    number (confidence interval 90%)
        Clinical Benefit Rate - RECIST v1.1
    33.3 (6.3 to 72.9)
    8.3 (0.4 to 33.9)
    0 (0.0 to 22.1)
    0 (0.0 to 20.6)
    0 (0.0 to 39.3)
    18.2 (3.3 to 47.0)
        Clinical Benefit Rate - irRC
    50.0 (15.3 to 84.7)
    8.3 (0.4 to 33.9)
    0 (0.0 to 22.1)
    7.7 (0.4 to 31.6)
    33.3 (6.3 to 72.9)
    18.2 (3.3 to 47.0)
    No statistical analyses for this end point

    Secondary: Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) - per irRC

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    End point title
    		 Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) - per irRC [32]
    End point description
    Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per immune related Response criteria (irRC)
    End point type
    Secondary
    End point timeframe
    4 years
    Notes
    [32] - 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: This endpoint only applied to phase II arms and not phase Ib arms.
    End point values
    		 Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    20
    20
    21
    20
    Units: Percentage of participants
        number (confidence interval 90%)
    20.0 (7.1 to 40.1)
    5.0 (0.3 to 21.6)
    19.0 (6.8 to 38.4)
    30.0 (14.0 to 50.8)
    No statistical analyses for this end point

    Secondary: Phase II: Bayesian inference of Clinical Benefit Rate - per irRC - mean

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    End point title
    		 Phase II: Bayesian inference of Clinical Benefit Rate - per irRC - mean [33]
    End point description
    Full Analysis Set. Since objective responses are rare in advanced pancreatic cancer and that long lasting stable disease is considered beneficial to patients, clinical benefit rate (confirmed objective response or SD>4 months) was used as the primary endpoint for antitumor activity in this study changed from objective response to for this patient population.
    End point type
    Secondary
    End point timeframe
    4 years
    Notes
    [33] - 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: This endpoint only applied to phase II arms and not phase Ib arms.
    End point values
    		 Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    0 [34]
    20
    0 [35]
    0 [36]
    Units: Percentage of participants
        arithmetic mean (confidence interval 90%)
    ( to )
    5.6 (0.4 to 15.3)
    ( to )
    ( to )
    Notes
    [34] - See the Bayesian inference of Overall Response rate - per irRC - mean results
    [35] - See the Bayesian inference of Overall Response rate - per irRC - mean results
    [36] - See the Bayesian inference of Overall Response rate - per irRC - mean results
    No statistical analyses for this end point

    Secondary: Phase 1b and Phase II: Progression Free Survival based on investigator assessment as per RECIST v1.1 and per immune related Response criteria (irRC) - using Kaplan-Meier method - Median

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    End point title
    		 Phase 1b and Phase II: Progression Free Survival based on investigator assessment as per RECIST v1.1 and per immune related Response criteria (irRC) - using Kaplan-Meier method - Median
    End point description
    Phase 1b and Phase II: Progression Free Survival based on investigator assessment as per RECIST v1.1 and per immune related Response criteria (irRC) - using Kaplan-Meier method - Median
    End point type
    Secondary
    End point timeframe
    Up to year 4
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    6
    12
    12
    13
    6
    11
    20
    20
    21
    20
    Units: months
    median (confidence interval 90%)
        Median PFS - per RECIST v1.1
    1.5 (1.1 to 14.8)
    1.3 (1.3 to 2.7)
    1.3 (0.8 to 1.3)
    1.1 (0.6 to 1.3)
    1.3 (0.5 to 4.0)
    1.2 (0.6 to 2.4)
    1.6 (1.4 to 2.8)
    1.3 (1.2 to 1.4)
    1.3 (1.2 to 1.4)
    2.4 (1.4 to 3.7)
        Median PFS - per iiRC
    8.2 (1.2 to 25.8)
    2.2 (1.3 to 2.7)
    1.3 (0.9 to 1.3)
    1.0 (0.5 to 1.3)
    1.3 (0.5 to 16.8)
    1.2 (0.7 to 2.4)
    1.6 (1.4 to 2.8)
    1.3 (1.2 to 1.5)
    1.3 (1.2 to 1.4)
    3.7 (1.4 to 4.2)
    No statistical analyses for this end point

    Secondary: Phase 1b and Phase II: Overall Survival - using Kaplan-Meier method - Median

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    End point title
    		 Phase 1b and Phase II: Overall Survival - using Kaplan-Meier method - Median
    End point description
    Phase 1b and Phase II: Overall Survival - using Kaplan-Meier method - Median
    End point type
    Secondary
    End point timeframe
    Up to year 4
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    6
    12
    12
    13
    6
    11
    20
    20
    21
    20
    Units: months
        median (confidence interval 90%)
    12.3 (3.1 to 26.6)
    9.6 (3.8 to 12.2)
    4.2 (1.5 to 7.9)
    2.8 (1.2 to 3.8)
    22.8 (1.1 to 26.8)
    5.7 (1.2 to 8.2)
    8.9 (5.6 to 16.6)
    2.6 (1.8 to 5.0)
    11.7 (9.2 to 14.6)
    19.7 (9.2 to 20.3)
    No statistical analyses for this end point

    Secondary: Phase 1b and Phase II: Duration of Response (DOR)

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    End point title
    		 Phase 1b and Phase II: Duration of Response (DOR)
    End point description
    Phase 1b and Phase II: Duration of Response (DOR) per RECIST v1.1 and per immune related Response criteria (irRC)
    End point type
    Secondary
    End point timeframe
    4 years
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    6
    12
    12
    13
    6
    11
    20
    20
    21
    20
    Units: days
    median (full range (min-max))
        Duration of response(days) - based on RECIST v1.1
    372.0 (372 to 372)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    155.0 (155.0 to 155.0)
    169 (169 to 169)
    999 (999 to 999)
    328.5 (194 to 463)
    999 (999 to 999)
        Duration of response(days) - based on irRC
    372.0 (372.0 to 372.0)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    155.0 (155.0 to 155.0)
    169 (169 to 169)
    999 (999 to 999)
    328.5 (194 to 463)
    999 (999 to 999)
    No statistical analyses for this end point

    Secondary: Phase 1b and Phase II: Disease Control Rate (DCR)

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    End point title
    		 Phase 1b and Phase II: Disease Control Rate (DCR)
    End point description
    Phase 1b and Phase II: Disease Control Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per RECIST v1.1 and per immune related Response criteria (irRC)
    End point type
    Secondary
    End point timeframe
    4 years
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    6
    12
    12
    13
    6
    11
    20
    20
    21
    20
    Units: Percentage
    number (confidence interval 90%)
        Disease Control Rate - RECIST v1.1
    33.3 (6.3 to 72.9)
    8.3 (0.4 to 33.9)
    0 (0.0 to 22.1)
    15.4 (2.8 to 41.0)
    16.7 (0.9 to 58.2)
    18.2 (3.3 to 47.0)
    20.0 (7.1 to 40.1)
    0 (0.0 to 13.9)
    19.0 (6.8 to 38.4)
    35.0 (17.7 to 55.8)
        Disease Control Rate -irRC
    50.0 (15.3 to 84.7)
    8.3 (0.4 to 33.9)
    0 (0.0 to 22.1)
    15.4 (2.8 to 41.0)
    33.3 (6.3 to 72.9)
    18.2 (3.3 to 47.0)
    20.0 (7.1 to 40.1)
    5.0 (0.3 to 21.6)
    19.0 (6.8 to 38.4)
    45.0 (25.9 to 65.3)
    No statistical analyses for this end point

    Secondary: Phase II: Percentage of participants with adverse events, as a measure of safety

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    End point title
    		 Phase II: Percentage of participants with adverse events, as a measure of safety [37]
    End point description
    Phase II: To further characterize the safety and tolerability of MCS110 given in combination with PDR001
    End point type
    Secondary
    End point timeframe
    From start of treatment to a maximum timeframe of 92.4 weeks for phase II.
    Notes
    [37] - 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: This endpoint only applied to phase II arms and not phase Ib arms.
    End point values
    		 Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    20
    20
    21
    20
    Units: Participants
        Adverse events - all grades
    20
    20
    21
    20
        AEs - Treatment-related - all grades
    16
    15
    17
    19
        SAEs - all grades
    8
    14
    8
    7
        SAEs - Treatment-related - all grades
    1
    4
    4
    1
        Fatal SAEs - all grades
    1
    1
    0
    1
        Fatal SAEs - Treatment-related - all grades
    0
    1
    0
    0
        AEs leading to disc.- all grades
    1
    1
    1
    2
        AEs leading to disc.- Treat-related - all grades
    1
    0
    1
    1
        AEs leading to dose adjust / interrupt-all grades
    11
    4
    8
    11
        AEs requiring addit.l therapy - all grades
    19
    18
    19
    17
    No statistical analyses for this end point

    Secondary: Phase Ib and Phase II: Immunogenicity MCS110

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    End point title
    		 Phase Ib and Phase II: Immunogenicity MCS110
    End point description
    Phase Ib and Phase II: Presence of anti-MCS110 antibodies
    End point type
    Secondary
    End point timeframe
    4 years
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    6
    12
    12
    13
    6
    11
    20
    20
    21
    20
    Units: Participants
        Baseline (B/l) positive
    0
    1
    1
    1
    0
    0
    0
    0
    0
    0
        Baseline negative
    6
    11
    11
    12
    6
    11
    19
    19
    17
    18
        Baseline missing
    0
    0
    0
    0
    0
    0
    1
    1
    4
    2
        B/l positive, on treatment persistent positive
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        B/l positive, on treatment only last positive
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
        Baseline positive, on treatment any positive
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Baseline positive, on treatment all negative
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
        B/l negative, on treatment persistent positive
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        B/l negative, on treatment only last positive
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        B/l negative, on treatment any positive
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Baseline negative, on treatment all negative
    5
    10
    8
    6
    5
    6
    12
    16
    14
    17
        B/l missing, on treatment persistent positive
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        B/l missing, on treatment only last positive
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        B/l missing, on treatment any positive
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        B/l missing, on treatment all negative
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Phase Ib and Phase II: Immunogenicity PDR001

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    End point title
    		 Phase Ib and Phase II: Immunogenicity PDR001
    End point description
    Phase Ib and Phase II: Presence of Anti-PDR001 antibodies
    End point type
    Secondary
    End point timeframe
    4 years
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    6
    12
    12
    13
    6
    11
    20
    20
    21
    20
    Units: Participants
        Baseline (B/l) positive
    0
    2
    1
    2
    1
    2
    1
    1
    0
    1
        Baseline negative
    6
    10
    11
    10
    5
    8
    18
    17
    19
    19
        Baseline missing
    0
    0
    0
    1
    0
    1
    1
    2
    2
    0
        B/l positive, on treatment persistent positive
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
        B/l positive, on treatment only last positive
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
        B/l positive, on treatment any positive
    0
    0
    0
    0
    1
    1
    1
    0
    0
    1
        Bl/ positive, on treatment all negative
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        B/l negative, on treatment persistent positive
    0
    1
    0
    0
    0
    1
    0
    0
    0
    1
        B/l negative, on treatment only last positive
    1
    1
    0
    0
    0
    1
    0
    4
    1
    0
        B/l negative, on treatment any positive
    1
    3
    1
    0
    0
    0
    0
    1
    0
    2
        B/l negative, on treatment all negative
    4
    4
    8
    6
    4
    2
    11
    10
    16
    13
        B/l missing, on treatment persistent positive
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        B/l missing, on treatment only last positive
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        B/l missing, on treatment any positive
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        B/l missing, on treatment all negative
    0
    0
    0
    1
    0
    1
    1
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Phase Ib and Phase II: Pharmacokinetics of MCS110 - AUClast and AUCinf

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    End point title
    		 Phase Ib and Phase II: Pharmacokinetics of MCS110 - AUClast and AUCinf
    End point description
    Phase Ib and Phase II: PK Parameters - AUClast, which is the AUC from time zero to the last measurable concentration sampling time (tlast) (mass × time × volume-1); and AUCinf, which is the AUC from time zero to infinity (mass × time × volume-1) - MCS110 (C1 = Cycle1; C4 = Cycle 4)
    End point type
    Secondary
    End point timeframe
    cycle 1 (day 21) and cycle 4 (day 84)
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    6
    11
    12
    13
    6
    11
    20
    19
    20
    20
    Units: day*ng/mL
    arithmetic mean (standard deviation)
        AUClast - C1-day 21(n=6,9,12,12,6,10,16,16,16,18)
    46900 ± 9080
    343000 ± 142000
    249000 ± 93400
    490000 ± 149000
    909000 ± 233000
    1090000 ± 231000
    1200000 ± 507000
    1090000 ± 352000
    1120000 ± 440000
    1270000 ± 335000
        AUCinf-C1-day 21(n=6,7,7,9,5,5,0,0,0,0)
    50100 ± 11600
    383000 ± 178000
    330000 ± 73400
    560000 ± 177000
    1020000 ± 336000
    988000 ± 116000
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
        AUClast C4-day 84(n=3,6,4,2,3,3,4,3,4,13)
    41000 ± 22800
    213000 ± 92200
    232000 ± 99300
    710000 ± 171000
    1520000 ± 353000
    1200000 ± 1030000
    1200000 ± 389000
    918000 ± 102000
    1010000 ± 337000
    1240000 ± 499000
        AUCinf-C4-day 84(n=3,4,4,1,0,1,0,0,0,0)
    42300 ± 21900
    260000 ± 73500
    253000 ± 114000
    619000 ± 999
    999 ± 999
    769000 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    No statistical analyses for this end point

    Secondary: Phase Ib and Phase II: Pharmacokinetics of PDR001 - AUClast and AUCinf

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    End point title
    		 Phase Ib and Phase II: Pharmacokinetics of PDR001 - AUClast and AUCinf
    End point description
    Phase Ib and Phase II: Pharmacokinetics (PK) Parameters - AUClast, which is the AUC from time zero to the last measurable concentration sampling time (tlast) (mass × time × volume-1); and AUCinf, which is the AUC from time zero to infinity (mass × time × volume-1) and AUCinf - PDR001. (C1 = Cycle1; C4 = Cycle 4)
    End point type
    Secondary
    End point timeframe
    cycle 1 (day 21) and cycle 4 (day 84)
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    6
    11
    12
    13
    6
    11
    20
    19
    20
    20
    Units: day*ug/mL
    arithmetic mean (standard deviation)
        AUClast- C1-day 21(n=6,11,11,13,6,11,20,18,19,18)
    229 ± 68.3
    271 ± 53.8
    651 ± 322
    604 ± 309
    581 ± 147
    450 ± 135
    825 ± 402
    782 ± 264
    764 ± 311
    782 ± 307
        AUCinf-C1-day 21(n=0,1,1,0,1,1,0,0,0,0)
    999 ± 999
    274 ± 999
    610 ± 999
    999 ± 999
    747 ± 999
    710 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
        AUClast-C4-day 84((n=3,6,4,2,3,3,5,3,4,13)
    369 ± 26.4
    330 ± 182
    1020 ± 526
    2020 ± 1170
    954 ± 179
    718 ± 288
    1170 ± 388
    1330 ± 555
    1660 ± 283
    1260 ± 533
        AUCinf -C4-day 84(n=0,1,0,0,0,0,0,0,0,0)
    999 ± 999
    196 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    No statistical analyses for this end point

    Secondary: Phase Ib and Phase II: Pharmacokinetics of MCS110 - Cmax and Clast

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    End point title
    		 Phase Ib and Phase II: Pharmacokinetics of MCS110 - Cmax and Clast
    End point description
    Phase Ib and Phase II: PK Parameters - Cmax, which is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass × volume-1); and Clast - MCS110. (C1 = Cycle1; C4 = Cycle 4)
    End point type
    Secondary
    End point timeframe
    cycle 1 (day 21) and cycle 4 (day 84)
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    6
    11
    12
    13
    6
    11
    20
    19
    20
    20
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cmax-C1-day 21(n=6,9,12,12,6,10,16,16,16,18)
    17400 ± 1870
    58800 ± 16900
    56700 ± 17800
    96900 ± 28600
    122000 ± 17100
    186000 ± 54000
    158000 ± 44800
    130000 ± 38400
    134000 ± 64900
    151000 ± 42500
        Clast-C1-day 21(n=6,9,12,12,6,10,16,16,16,18)
    1120 ± 795
    1290 ± 2760
    6600 ± 6370
    9130 ± 11500
    15100 ± 9070
    28700 ± 27800
    33000 ± 21300
    12900 ± 10700
    24500 ± 20100
    17500 ± 11400
        Cmax-C4-day 84(n=3,6,4,2,3,3,4,3,4,13)
    13500 ± 5580
    53000 ± 9790
    48900 ± 14100
    76400 ± 24000
    176000 ± 19800
    189000 ± 29400
    159000 ± 39800
    152000 ± 58000
    128000 ± 42600
    147000 ± 38300
        Clast-C4-day 84(n=3,6,4,2,3,3,4,3,4,13)
    510 ± 457
    5700 ± 10300
    3490 ± 2410
    7350 ± 5870
    45100 ± 12400
    34100 ± 29800
    57600 ± 45000
    33300 ± 42600
    18600 ± 21700
    29400 ± 20700
    No statistical analyses for this end point

    Secondary: Phase Ib and Phase II: Pharmacokinetics of PDR001 - Cmax and Clast

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    End point title
    		 Phase Ib and Phase II: Pharmacokinetics of PDR001 - Cmax and Clast
    End point description
    Phase Ib and Phase II: PK Parameters - Cmax, which is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass × volume-1); and Clast - PDR001. (C1 = Cycle1; C4 = Cycle 4)
    End point type
    Secondary
    End point timeframe
    cycle 1 (day 21) and cycle 4 (day 84)
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    6
    11
    12
    13
    6
    11
    20
    19
    20
    20
    Units: ug/mL
    arithmetic mean (standard deviation)
        Cmax-C1-day 21(n=6,11,11,13,6,11,20,18,19,18)
    24 ± 9.52
    29.5 ± 6.56
    73.4 ± 22.3
    77 ± 24.3
    76.6 ± 36.8
    64.2 ± 20.4
    94.5 ± 27.4
    75.3 ± 23.9
    80.2 ± 24
    70.3 ± 21.6
        Clast -C1-day 21(n=6,11,11,13,6,11,20,18,19,18)
    7.73 ± 2.97
    7.24 ± 2.95
    19.4 ± 11.7
    26.4 ± 11.8
    22.7 ± 12.8
    17.2 ± 8.67
    34.5 ± 13.3
    24 ± 12
    22.8 ± 9.44
    24.4 ± 14.6
        Cmax-C4-day 84(n=3,6,4,2,3,3,5,3,4,13)
    29.5 ± 9.3
    36.8 ± 10.5
    126 ± 54.6
    153 ± 22.6
    92 ± 22.1
    85.9 ± 16.8
    123 ± 56.8
    127 ± 7
    122 ± 23.6
    108 ± 23.4
        Clast-C4-day 84(n=3,6,4,2,3,3,5,3,4,13)
    10.7 ± 2.25
    14.5 ± 8.47
    65.1 ± 37.6
    71 ± 6.65
    47.5 ± 25.7
    35.6 ± 14.7
    81.4 ± 43.6
    62.1 ± 9.93
    48.8 ± 20.6
    51.3 ± 23.7
    No statistical analyses for this end point

    Secondary: Phase Ib and Phase II: Pharmacokinetics of MCS110 - Tmax

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    End point title
    		 Phase Ib and Phase II: Pharmacokinetics of MCS110 - Tmax
    End point description
    Phase Ib and Phase II: PK Parameters - Tmax, which is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time) - MCS110. (C1 = Cycle1; C4 = Cycle 4)
    End point type
    Secondary
    End point timeframe
    cycle 1 (day 21) and cycle 4 (day 84)
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    6
    11
    12
    13
    6
    11
    20
    19
    20
    20
    Units: hour
    median (full range (min-max))
        Tmax -C1-day 21(n=6,9,12,12,6,10,16,16,16,18)
    2.02 (1.5 to 2.08)
    1.92 (0.5 to 23.7)
    2.08 (1.5 to 22.2)
    2.13 (1.92 to 24)
    2.06 (2 to 24.4)
    2.04 (1.92 to 26.2)
    2.01 (0.5 to 162)
    2.08 (1.92 to 2.28)
    2.09 (2 to 163)
    2.08 (1.5 to 188)
        Tmax-C4-day 84(n=3,6,4,2,3,3,4,3,4,13)
    2 (2 to 2)
    2.05 (0.5 to 2.08)
    2.03 (2 to 23.7)
    13 (2.02 to 24)
    2 (2 to 20.8)
    2.03 (1.98 to 21.3)
    2 (1.92 to 2.12)
    2.02 (1.98 to 2.08)
    2.04 (2 to 2.12)
    2.05 (2 to 2.13)
    No statistical analyses for this end point

    Secondary: Phase Ib and Phase II: Pharmacokinetics of PDR001 - Tmax

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    End point title
    		 Phase Ib and Phase II: Pharmacokinetics of PDR001 - Tmax
    End point description
    Phase Ib and Phase II: PK Parameters - Tmax, which is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time) - PDR001. (C1 = Cycle1; C4 = Cycle 4)
    End point type
    Secondary
    End point timeframe
    cycle 1 (day 21) and cycle 4 (day 84)
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    6
    11
    12
    13
    6
    11
    20
    19
    20
    20
    Units: hour
    median (full range (min-max))
        Tmax-C1-day 21(n=6,11,11,13,6,11,20,18,19,18)
    11.5 (1.48 to 26)
    2.08 (1.5 to 25.5)
    1.53 (1 to 26.5)
    1.57 (1.5 to 22.3)
    1.53 (0.983 to 25.8)
    1.52 (1.5 to 22.8)
    1.5 (1 to 168)
    1.5 (0.5 to 3.22)
    1.5 (1.42 to 166)
    1.5 (1.45 to 624)
        Tmax-C4-day 84(n=3,6,4,2,3,3,5,3,4,13)
    1.52 (1.5 to 22.4)
    1.53 (0 to 23.7)
    1.2 (0 to 1.5)
    1.57 (1.55 to 1.58)
    1.5 (1.5 to 3.42)
    1.45 (1.43 to 2.92)
    1.53 (1.5 to 165)
    1.47 (1.42 to 1.48)
    1.54 (1.48 to 1.62)
    1.5 (1.43 to 1.67)
    No statistical analyses for this end point

    Secondary: Phase Ib and Phase II: Pharmacokinetics of MCS110 - T1/2

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    End point title
    		 Phase Ib and Phase II: Pharmacokinetics of MCS110 - T1/2
    End point description
    Phase Ib and Phase II: PK Parameters - T1/2, which is the terminal half-life associated with the terminal slope of a semi logarithmic concentration time curve (time) - MCS110. (C1 = Cycle1; C4 = Cycle 4)
    End point type
    Secondary
    End point timeframe
    cycle 1 (day 21) and cycle 4 (day 84)
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    6
    11
    12
    13
    6
    11
    20
    19
    20
    20
    Units: day
    median (full range (min-max))
        T1/2-C1-day 21(n=6,7,7,9,5,5,0,0,0,0)
    1.5 (1.25 to 2.38)
    2.16 (1.68 to 6.71)
    3.3 (1.85 to 5.32)
    3.48 (1.73 to 7.82)
    6.35 (2.17 to 8.05)
    4.36 (2.25 to 6.62)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
        T1/2-C4- day 84(n=3,4,4,1,0,1,0,0,0,0)
    1.77 (1.23 to 1.81)
    1.53 (1.03 to 2.49)
    4.08 (1.41 to 4.26)
    6.32 (6.32 to 6.32)
    999 (999 to 999)
    4.82 (4.82 to 4.82)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    No statistical analyses for this end point

    Secondary: Phase Ib and Phase II: Pharmacokinetics of PDR001 - T1/2

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    End point title
    		 Phase Ib and Phase II: Pharmacokinetics of PDR001 - T1/2
    End point description
    Phase Ib and Phase II: PK Parameters - T1/2, which is the terminal half-life associated with the terminal slope of a semi logarithmic concentration time curve (time) - PDR001. (C1 = Cycle1; C4 = Cycle 4)
    End point type
    Secondary
    End point timeframe
    cycle 1 (day 21) and cycle 4 (day 84)
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    6
    11
    12
    13
    6
    11
    20
    19
    20
    20
    Units: day
    median (full range (min-max))
        T1/2 -C1-day 21(n=0,1,1,0,1,1,0,0,0,0)
    999 (999 to 999)
    8.14 (8.14 to 8.14)
    7.71 (7.71 to 7.71)
    999 (999 to 999)
    7.13 (7.13 to 7.13)
    7.33 (7.33 to 7.33)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
        T1/2-C4-day 84(n=0,1,0,0,0,0,0,0,0,0)
    999 (999 to 999)
    7.81 (7.81 to 7.81)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    No statistical analyses for this end point

    Secondary: Phase Ib and Phase II: Pharmacokinetics of MCS110 - CL

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    End point title
    		 Phase Ib and Phase II: Pharmacokinetics of MCS110 - CL
    End point description
    Phase Ib and Phase II: PK Parameters - CL, which is the total body clearance of drug from the plasma (volume × time-1) - MCS110. (C1 = Cycle1; C4 = Cycle 4)
    End point type
    Secondary
    End point timeframe
    cycle 1 (day 21) and cycle 4 (day 84)
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    6
    11
    12
    13
    6
    11
    20
    19
    20
    20
    Units: L/h/kg
    arithmetic mean (standard deviation)
        CL -C1- day 21(n=6,7,7,9,5,5,0,0,0,0)
    0.000863 ± 0.000158
    0.000388 ± 0.000181
    0.000394 ± 0.0000833
    0.000407 ± 0.000131
    0.000338 ± 0.000117
    0.000427 ± 0.0000558
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
        CL-C4-day 84(n=3,4,4,1,0,1,0,0,0,0)
    0.00117 ± 0.000549
    0.000523 ± 0.000199
    0.000315 ± 0.000218
    0.000337 ± 999
    999 ± 999
    0.000541 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    No statistical analyses for this end point

    Secondary: Phase Ib and Phase II: Pharmacokinetics of PDR001 - CL

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    End point title
    		 Phase Ib and Phase II: Pharmacokinetics of PDR001 - CL
    End point description
    Phase Ib and Phase II: PK Parameters - CL, which is the total body clearance of drug from the plasma (volume × time-1) - PDR001. (C1 = Cycle1; C4 = Cycle 4)
    End point type
    Secondary
    End point timeframe
    cycle 1 (day 21) and cycle 4 (day 84)
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    6
    11
    12
    13
    6
    11
    20
    19
    20
    20
    Units: L/h
    arithmetic mean (standard deviation)
        CL-C1-day 21(n=0,1,1,0,1,1,0,0,0,0)
    999 ± 999
    0.0152 ± 999
    0.0205 ± 999
    999 ± 999
    0.0167 ± 999
    0.0176 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
        CL-C4-day 84(n=0,1,0,0,0,0,0,0,0,0)
    999 ± 999
    0.0213 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    No statistical analyses for this end point

    Secondary: Phase Ib and Phase II: Pharmacokinetics of MCS110 - Vz

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    End point title
    		 Phase Ib and Phase II: Pharmacokinetics of MCS110 - Vz
    End point description
    Phase Ib and Phase II: PK Parameters - Vz, which is the apparent volume of distribution during terminal phase (volume) - MCS110. (C1 = Cycle1; C4 = Cycle 4)
    End point type
    Secondary
    End point timeframe
    cycle 1 (day 21) and cycle 4 (day 84)
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    6
    11
    12
    13
    6
    11
    20
    19
    20
    20
    Units: L/kg
    arithmetic mean (standard deviation)
        Vz-C1-day 21(n=6,7,7,9,5,5,0,0,0,0)
    0.0486 ± 0.00989
    0.0334 ± 0.00783
    0.0423 ± 0.00875
    0.051 ± 0.0206
    0.0651 ± 0.0201
    0.065 ± 0.0267
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
        Vz-C4-day 84(n=3,4,4,1,0,1,0,0,0,0)
    0.0684 ± 0.0407
    0.0294 ± 0.0128
    0.045 ± 0.0308
    0.0736 ± 999
    999 ± 999
    0.0904 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    No statistical analyses for this end point

    Secondary: Phase Ib and Phase II: Pharmacokinetics of PDR001 - Vz

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    End point title
    		 Phase Ib and Phase II: Pharmacokinetics of PDR001 - Vz
    End point description
    Phase Ib and Phase II: PK Parameters - Vz, which is the apparent volume of distribution during terminal phase (volume) - PDR001. (C1 = Cycle1; C4 = Cycle 4)
    End point type
    Secondary
    End point timeframe
    cycle 1 (day 21) and cycle 4 (day 84)
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    6
    11
    12
    13
    6
    11
    20
    19
    20
    20
    Units: Liters (L)
    arithmetic mean (standard deviation)
        Vz-C1-day 21(n=0,1,1,0,1,1,0,0,0,0)
    999 ± 999
    4.28 ± 999
    5.47 ± 999
    999 ± 999
    4.13 ± 999
    4.47 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
        Vz-C4- day 84(n=0,1,0,0,0,0,0,0,0,0)
    999 ± 999
    5.76 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    999 ± 999
    No statistical analyses for this end point

    Secondary: Phase Ib and Phase II: Pharmacokinetics of MCS110 - Accumulation ratio (AR)

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    End point title
    		 Phase Ib and Phase II: Pharmacokinetics of MCS110 - Accumulation ratio (AR)
    End point description
    Phase Ib and Phase II: PK Parameters - Accumulation ratio (AR), which is the AUClast (multiple Dose)/AUClast (single dose) (for cycle 4 only) - MCS110
    End point type
    Secondary
    End point timeframe
    cycle 4 (day 84)
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    3
    6
    4
    2
    3
    3
    4
    3
    4
    12
    Units: Ratio of AUC
        arithmetic mean (standard deviation)
    0.789 ± 0.232
    0.744 ± 0.307
    0.833 ± 0.0739
    1.14 ± 0.0991
    1.37 ± 0.278
    1.04 ± 0.731
    0.712 ± 0.205
    0.829 ± 0.177
    0.723 ± 0.315
    0.987 ± 0.35
    No statistical analyses for this end point

    Secondary: Phase Ib and Phase II: Pharmacokinetics of PDR001 - Accumulation ratio (AR)

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    End point title
    		 Phase Ib and Phase II: Pharmacokinetics of PDR001 - Accumulation ratio (AR)
    End point description
    Phase Ib and Phase II: PK Parameters - Accumulation ratio (AR), which is the AUClast (multiple Dose)/AUClast (single dose) (for cycle 4 only) - PDR001
    End point type
    Secondary
    End point timeframe
    cycle 4 (day 84)
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    3
    6
    4
    2
    3
    3
    5
    3
    4
    13
    Units: Ratio of AUC
        arithmetic mean (standard deviation)
    1.48 ± 0.17
    1.15 ± 0.522
    1.14 ± 0.176
    1.89 ± 0.84
    1.85 ± 0.348
    1.5 ± 0.848
    1.08 ± 0.235
    1.56 ± 0.593
    2.05 ± 0.156
    1.54 ± 0.664
    No statistical analyses for this end point

    Post-hoc: Phase Ib and Phase II: All Collected Deaths

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    End point title
    		 Phase Ib and Phase II: All Collected Deaths
    End point description
    On treatment deaths are reported from the start of treatment until end of study treatment plus 30 days, up to maximum duration of 116.4 weeks for phase Ib and 92.4 weeks for phase II. Deaths post treatment survival follow up are reported after the on-treatment period, up to a maximum timeframe of 46 months (3.8 years).
    End point type
    Post-hoc
    End point timeframe
    For ontreatment deaths: up to maximum timeframe of 116.4 weeks for phase Ib and 92.4 weeks for phase II. For total deaths: up to 3.8 years
    End point values
    		 Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Number of subjects analysed
    6
    12
    12
    13
    6
    11
    20
    20
    21
    20
    Units: Participants
        Total Deaths
    6
    12
    10
    12
    4
    10
    11
    19
    14
    11
        On-treatment Deaths
    0
    1
    4
    4
    1
    4
    1
    3
    0
    2
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    On-treatment adverse events are reported, from first dose of study treatment until end of study treatment plus 30 days, up to maximum timeframe of 116.4 weeks for phase Ib and 92.4 weeks for phase II.
    Adverse event reporting additional description
    Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Ph Ib: MCS110@1 mg/kg Q3W@+ PDR001 100@mg Q3W
    Reporting group description
    		 Ph Ib: MCS110@1 mg/kg Q3W@+ PDR001 100@mg Q3W

    Reporting group title
    Ph Ib: MCS110@3 mg/kg Q3W@+ PDR001 300@mg Q3W
    Reporting group description
    		 Ph Ib: MCS110@3 mg/kg Q3W@+ PDR001 300@mg Q3W

    Reporting group title
    Ph Ib: MCS110@5 mg/kg Q3W@+ PDR001 300@mg Q3W
    Reporting group description
    		 Ph Ib: MCS110@5 mg/kg Q3W@+ PDR001 300@mg Q3W

    Reporting group title
    Ph Ib: MCS110@3 mg/kg Q3W@+ PDR001 100@mg Q3W
    Reporting group description
    		 Ph Ib: MCS110@3 mg/kg Q3W@+ PDR001 100@mg Q3W

    Reporting group title
    Ph Ib: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W
    Reporting group description
    		 Ph Ib: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W

    Reporting group title
    Ph Ib: MCS110@10 mg/kg Q3W@+ PDR001 300@mg Q3W
    Reporting group description
    		 Ph Ib: MCS110@10 mg/kg Q3W@+ PDR001 300@mg Q3W

    Reporting group title
    Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - TNBC
    Reporting group description
    		 Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - TNBC

    Reporting group title
    Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - PC
    Reporting group description
    		 Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - PC

    Reporting group title
    Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - EC
    Reporting group description
    		 Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - EC

    Reporting group title
    Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - ME
    Reporting group description
    		 Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - ME

    Serious adverse events
    		 Ph Ib: MCS110@1 mg/kg Q3W@+ PDR001 100@mg Q3W Ph Ib: MCS110@3 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@5 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@3 mg/kg Q3W@+ PDR001 100@mg Q3W Ph Ib: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@10 mg/kg Q3W@+ PDR001 300@mg Q3W Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - TNBC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - PC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - EC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - ME
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 6 (50.00%)
    4 / 12 (33.33%)
    7 / 13 (53.85%)
    4 / 12 (33.33%)
    2 / 6 (33.33%)
    5 / 11 (45.45%)
    8 / 20 (40.00%)
    14 / 20 (70.00%)
    8 / 21 (38.10%)
    7 / 20 (35.00%)
         number of deaths (all causes)
    0
    4
    4
    1
    1
    4
    1
    3
    0
    2
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Infected neoplasm
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Lymphangiosis carcinomatosa
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Tumour pain
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    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 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 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
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    0 / 0
    Generalised oedema
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    2 / 13 (15.38%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    2 / 20 (10.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    1 / 1
    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
    0 / 0
    0 / 0
    0 / 0
    Ulcer
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    2 / 20 (10.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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 / 1
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device breakage
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Gastrointestinal procedural complication
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 1
    Infusion related reaction
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral infarction
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Guillain-Barre syndrome
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 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
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    2 / 20 (10.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Haemoperitoneum
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct obstruction
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Jaundice cholestatic
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash papular
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Anuria
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    1 / 1
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Fistula
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Flank pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cystitis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    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 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Hypophosphataemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Ph Ib: MCS110@1 mg/kg Q3W@+ PDR001 100@mg Q3W Ph Ib: MCS110@3 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@5 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@3 mg/kg Q3W@+ PDR001 100@mg Q3W Ph Ib: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@10 mg/kg Q3W@+ PDR001 300@mg Q3W Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - TNBC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - PC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - EC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - ME
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 6 (100.00%)
    12 / 12 (100.00%)
    13 / 13 (100.00%)
    12 / 12 (100.00%)
    6 / 6 (100.00%)
    11 / 11 (100.00%)
    20 / 20 (100.00%)
    20 / 20 (100.00%)
    21 / 21 (100.00%)
    20 / 20 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    1
    Metastases to central nervous system
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Tumour pain
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    3 / 21 (14.29%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    3
    1
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    Hypertension
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    1 / 13 (7.69%)
    1 / 12 (8.33%)
    1 / 6 (16.67%)
    1 / 11 (9.09%)
    1 / 20 (5.00%)
    1 / 20 (5.00%)
    2 / 21 (9.52%)
    4 / 20 (20.00%)
         occurrences all number
    0
    1
    1
    1
    1
    1
    1
    2
    2
    4
    General disorders and administration site conditions
    Adverse reaction
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Asthenia
         subjects affected / exposed
    3 / 6 (50.00%)
    3 / 12 (25.00%)
    3 / 13 (23.08%)
    5 / 12 (41.67%)
    3 / 6 (50.00%)
    5 / 11 (45.45%)
    2 / 20 (10.00%)
    3 / 20 (15.00%)
    2 / 21 (9.52%)
    3 / 20 (15.00%)
         occurrences all number
    3
    3
    3
    5
    3
    5
    2
    4
    2
    3
    Chest discomfort
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Chills
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 12 (16.67%)
    2 / 13 (15.38%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    4 / 20 (20.00%)
    3 / 21 (14.29%)
    7 / 20 (35.00%)
         occurrences all number
    1
    3
    2
    1
    0
    0
    1
    4
    3
    10
    Face oedema
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 12 (16.67%)
    3 / 13 (23.08%)
    2 / 12 (16.67%)
    1 / 6 (16.67%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    3 / 21 (14.29%)
    6 / 20 (30.00%)
         occurrences all number
    0
    2
    3
    2
    1
    1
    0
    1
    3
    8
    Fatigue
         subjects affected / exposed
    2 / 6 (33.33%)
    5 / 12 (41.67%)
    2 / 13 (15.38%)
    3 / 12 (25.00%)
    2 / 6 (33.33%)
    0 / 11 (0.00%)
    5 / 20 (25.00%)
    2 / 20 (10.00%)
    4 / 21 (19.05%)
    4 / 20 (20.00%)
         occurrences all number
    2
    5
    2
    3
    3
    0
    6
    2
    5
    5
    Gait disturbance
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    General physical health deterioration
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    1 / 13 (7.69%)
    1 / 12 (8.33%)
    2 / 6 (33.33%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    1
    1
    2
    0
    0
    0
    0
    0
    Generalised oedema
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    Influenza like illness
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 12 (16.67%)
    0 / 13 (0.00%)
    3 / 12 (25.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    2 / 20 (10.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    1
    2
    0
    3
    0
    0
    2
    1
    0
    1
    Oedema peripheral
         subjects affected / exposed
    2 / 6 (33.33%)
    2 / 12 (16.67%)
    2 / 13 (15.38%)
    1 / 12 (8.33%)
    1 / 6 (16.67%)
    1 / 11 (9.09%)
    2 / 20 (10.00%)
    3 / 20 (15.00%)
    3 / 21 (14.29%)
    3 / 20 (15.00%)
         occurrences all number
    3
    2
    3
    1
    1
    1
    2
    3
    3
    3
    Pyrexia
         subjects affected / exposed
    1 / 6 (16.67%)
    3 / 12 (25.00%)
    1 / 13 (7.69%)
    4 / 12 (33.33%)
    0 / 6 (0.00%)
    5 / 11 (45.45%)
    4 / 20 (20.00%)
    4 / 20 (20.00%)
    1 / 21 (4.76%)
    8 / 20 (40.00%)
         occurrences all number
    1
    3
    1
    6
    0
    7
    6
    6
    1
    10
    Suprapubic pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Immune system disorders
    Cytokine release syndrome
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Reproductive system and breast disorders
    Breast pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    2 / 20 (10.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    Metrorrhagia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Varicocele
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Aphonia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Cough
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    3 / 12 (25.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    1 / 20 (5.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    0
    0
    4
    0
    1
    1
    1
    0
    1
    Dysphonia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    Dyspnoea
         subjects affected / exposed
    2 / 6 (33.33%)
    2 / 12 (16.67%)
    1 / 13 (7.69%)
    2 / 12 (16.67%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    2 / 20 (10.00%)
    1 / 20 (5.00%)
    3 / 21 (14.29%)
    1 / 20 (5.00%)
         occurrences all number
    2
    2
    1
    3
    1
    0
    2
    1
    3
    1
    Epistaxis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Haemoptysis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    1
    1
    Lung opacity
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Nasal congestion
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    Nasal mucosal ulcer
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    Pleural effusion
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    1 / 20 (5.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    1
    1
    0
    Pneumonitis
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Productive cough
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    2
    2
    0
    0
    0
    0
    0
    0
    Pulmonary embolism
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    1
    0
    1
    1
    0
    Respiratory failure
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Rhinalgia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    1 / 20 (5.00%)
    3 / 21 (14.29%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    1
    0
    1
    0
    1
    1
    3
    0
    Confusional state
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Depression
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    1
    1
    0
    Disorientation
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Eating disorder
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Insomnia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    2 / 12 (16.67%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    3 / 20 (15.00%)
    1 / 20 (5.00%)
    2 / 21 (9.52%)
    1 / 20 (5.00%)
         occurrences all number
    2
    0
    0
    2
    0
    0
    3
    1
    2
    2
    Investigations
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 12 (16.67%)
    1 / 13 (7.69%)
    1 / 12 (8.33%)
    1 / 6 (16.67%)
    2 / 11 (18.18%)
    4 / 20 (20.00%)
    5 / 20 (25.00%)
    7 / 21 (33.33%)
    4 / 20 (20.00%)
         occurrences all number
    1
    2
    1
    1
    3
    2
    8
    5
    11
    6
    Amylase increased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    2 / 20 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Aspartate aminotransferase increased
         subjects affected / exposed
    4 / 6 (66.67%)
    3 / 12 (25.00%)
    5 / 13 (38.46%)
    3 / 12 (25.00%)
    3 / 6 (50.00%)
    4 / 11 (36.36%)
    9 / 20 (45.00%)
    7 / 20 (35.00%)
    13 / 21 (61.90%)
    10 / 20 (50.00%)
         occurrences all number
    5
    3
    6
    3
    3
    4
    14
    7
    18
    11
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 12 (25.00%)
    2 / 13 (15.38%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    2 / 20 (10.00%)
    3 / 20 (15.00%)
    3 / 21 (14.29%)
    3 / 20 (15.00%)
         occurrences all number
    0
    3
    2
    0
    0
    0
    2
    3
    3
    4
    Blood bilirubin increased
         subjects affected / exposed
    3 / 6 (50.00%)
    2 / 12 (16.67%)
    2 / 13 (15.38%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    5
    2
    2
    0
    0
    0
    0
    0
    0
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 6 (16.67%)
    3 / 12 (25.00%)
    3 / 13 (23.08%)
    3 / 12 (25.00%)
    4 / 6 (66.67%)
    3 / 11 (27.27%)
    9 / 20 (45.00%)
    10 / 20 (50.00%)
    12 / 21 (57.14%)
    14 / 20 (70.00%)
         occurrences all number
    1
    3
    3
    4
    4
    3
    14
    10
    12
    15
    Blood creatinine increased
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    2 / 12 (16.67%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    2 / 21 (9.52%)
    1 / 20 (5.00%)
         occurrences all number
    3
    1
    0
    2
    0
    0
    0
    0
    2
    3
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    1 / 11 (9.09%)
    3 / 20 (15.00%)
    1 / 20 (5.00%)
    2 / 21 (9.52%)
    5 / 20 (25.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    3
    1
    2
    5
    Blood pressure increased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    C-reactive protein increased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    1
    0
    0
    0
    0
    Lipase increased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    2 / 20 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    3
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    2 / 20 (10.00%)
    2 / 20 (10.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    3
    2
    0
    2
    Neutrophil count increased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Platelet count decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    2 / 20 (10.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    2
    Transaminases increased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Weight decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    2 / 20 (10.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    2
    0
    1
    Injury, poisoning and procedural complications
    Abdominal injury
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Fall
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Foot fracture
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
    Infusion related reaction
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    3 / 12 (25.00%)
    1 / 6 (16.67%)
    1 / 11 (9.09%)
    3 / 20 (15.00%)
    2 / 20 (10.00%)
    3 / 21 (14.29%)
    1 / 20 (5.00%)
         occurrences all number
    1
    1
    0
    3
    1
    1
    3
    2
    3
    1
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Post procedural inflammation
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Procedural pain
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    1
    0
    0
    0
    Rib fracture
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Nervous system disorders
    Balance disorder
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Dizziness
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    2 / 13 (15.38%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    2 / 21 (9.52%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    2
    2
    0
    0
    1
    0
    2
    1
    Dysgeusia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    2 / 12 (16.67%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    1
    0
    1
    0
    0
    Headache
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 12 (8.33%)
    1 / 13 (7.69%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    5 / 20 (25.00%)
    0 / 20 (0.00%)
    3 / 21 (14.29%)
    1 / 20 (5.00%)
         occurrences all number
    1
    1
    1
    2
    0
    0
    7
    0
    7
    1
    Hypoaesthesia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    2 / 20 (10.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    2
    0
    0
    Paraesthesia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    1
    0
    0
    0
    0
    Somnolence
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 12 (25.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    0
    0
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 6 (66.67%)
    3 / 12 (25.00%)
    3 / 13 (23.08%)
    2 / 12 (16.67%)
    3 / 6 (50.00%)
    3 / 11 (27.27%)
    4 / 20 (20.00%)
    6 / 20 (30.00%)
    5 / 21 (23.81%)
    7 / 20 (35.00%)
         occurrences all number
    8
    4
    4
    2
    3
    4
    6
    9
    6
    8
    Leukocytosis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    2 / 13 (15.38%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    0
    1
    Eye disorders
    Dry eye
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    1
    1
    Eye pruritus
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    2 / 12 (16.67%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    0
    0
    0
    0
    0
    Eyelid oedema
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    1 / 13 (7.69%)
    3 / 12 (25.00%)
    0 / 6 (0.00%)
    2 / 11 (18.18%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    1
    3
    0
    2
    1
    0
    0
    0
    Lacrimation increased
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    4 / 12 (33.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    1
    0
    1
    4
    0
    0
    1
    0
    0
    1
    Panophthalmitis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Periorbital oedema
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 12 (16.67%)
    1 / 13 (7.69%)
    3 / 12 (25.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    3 / 20 (15.00%)
    3 / 20 (15.00%)
    4 / 21 (19.05%)
    6 / 20 (30.00%)
         occurrences all number
    0
    2
    1
    3
    1
    0
    3
    3
    4
    6
    Uveitis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Visual impairment
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
    Xerophthalmia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Abdominal distension
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    1
    0
    0
    Abdominal pain
         subjects affected / exposed
    2 / 6 (33.33%)
    3 / 12 (25.00%)
    3 / 13 (23.08%)
    3 / 12 (25.00%)
    1 / 6 (16.67%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    3 / 20 (15.00%)
    3 / 21 (14.29%)
    1 / 20 (5.00%)
         occurrences all number
    2
    4
    3
    3
    1
    1
    0
    3
    3
    1
    Abdominal pain lower
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    3 / 20 (15.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    1
    3
    1
    0
    0
    Aphthous ulcer
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Ascites
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    1 / 12 (8.33%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    1
    1
    2
    0
    0
    0
    0
    0
    Colitis
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Constipation
         subjects affected / exposed
    3 / 6 (50.00%)
    2 / 12 (16.67%)
    2 / 13 (15.38%)
    2 / 12 (16.67%)
    2 / 6 (33.33%)
    1 / 11 (9.09%)
    6 / 20 (30.00%)
    4 / 20 (20.00%)
    4 / 21 (19.05%)
    5 / 20 (25.00%)
         occurrences all number
    3
    2
    2
    2
    2
    1
    6
    4
    5
    5
    Diarrhoea
         subjects affected / exposed
    3 / 6 (50.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    1 / 12 (8.33%)
    2 / 6 (33.33%)
    3 / 11 (27.27%)
    2 / 20 (10.00%)
    4 / 20 (20.00%)
    2 / 21 (9.52%)
    1 / 20 (5.00%)
         occurrences all number
    6
    0
    1
    3
    2
    4
    2
    4
    2
    1
    Dry mouth
         subjects affected / exposed
    2 / 6 (33.33%)
    2 / 12 (16.67%)
    1 / 13 (7.69%)
    2 / 12 (16.67%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences all number
    2
    2
    1
    2
    0
    1
    0
    0
    1
    0
    Dyspepsia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    2 / 13 (15.38%)
    1 / 12 (8.33%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    2
    1
    1
    0
    1
    0
    1
    1
    Epigastric discomfort
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Flatulence
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    0
    0
    0
    1
    0
    Gastritis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Gingival bleeding
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Haematochezia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Melaena
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Nausea
         subjects affected / exposed
    2 / 6 (33.33%)
    3 / 12 (25.00%)
    5 / 13 (38.46%)
    5 / 12 (41.67%)
    1 / 6 (16.67%)
    6 / 11 (54.55%)
    6 / 20 (30.00%)
    8 / 20 (40.00%)
    6 / 21 (28.57%)
    4 / 20 (20.00%)
         occurrences all number
    2
    3
    6
    6
    1
    6
    6
    8
    8
    4
    Odynophagia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Stomatitis
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 12 (8.33%)
    3 / 13 (23.08%)
    1 / 12 (8.33%)
    1 / 6 (16.67%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    1 / 21 (4.76%)
    3 / 20 (15.00%)
         occurrences all number
    2
    1
    3
    1
    1
    1
    0
    1
    1
    3
    Vomiting
         subjects affected / exposed
    1 / 6 (16.67%)
    3 / 12 (25.00%)
    5 / 13 (38.46%)
    5 / 12 (41.67%)
    1 / 6 (16.67%)
    1 / 11 (9.09%)
    3 / 20 (15.00%)
    4 / 20 (20.00%)
    2 / 21 (9.52%)
    0 / 20 (0.00%)
         occurrences all number
    2
    4
    5
    5
    1
    1
    5
    6
    2
    0
    Hepatobiliary disorders
    Cholestasis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Portal vein thrombosis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Dry skin
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 12 (16.67%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    2
    0
    0
    0
    0
    1
    1
    0
    0
    Hair colour changes
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Hyperhidrosis
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Intertrigo
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Nail dystrophy
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Petechiae
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Pruritus
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 12 (16.67%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    2 / 20 (10.00%)
    2 / 20 (10.00%)
    2 / 21 (9.52%)
    1 / 20 (5.00%)
         occurrences all number
    1
    2
    0
    1
    1
    0
    2
    2
    2
    1
    Rash
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 12 (16.67%)
    0 / 13 (0.00%)
    2 / 12 (16.67%)
    1 / 6 (16.67%)
    1 / 11 (9.09%)
    3 / 20 (15.00%)
    2 / 20 (10.00%)
    2 / 21 (9.52%)
    4 / 20 (20.00%)
         occurrences all number
    0
    2
    0
    4
    1
    1
    3
    3
    4
    6
    Rash maculo-papular
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    2 / 21 (9.52%)
    2 / 20 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    2
    2
    Rash pruritic
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    Renal and urinary disorders
    Choluria
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Dysuria
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    1
    0
    Haematuria
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    1
    1
    Pollakiuria
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Proteinuria
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    2 / 21 (9.52%)
    2 / 20 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    3
    Renal colic
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Renal failure
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Ureterolithiasis
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Endocrine disorders
    Hypopituitarism
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Hypothyroidism
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    1 / 6 (16.67%)
    2 / 11 (18.18%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    1
    1
    2
    0
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 12 (8.33%)
    1 / 13 (7.69%)
    3 / 12 (25.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    3 / 20 (15.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
         occurrences all number
    1
    2
    1
    6
    3
    0
    3
    0
    1
    1
    Arthritis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Back pain
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    2 / 12 (16.67%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    2 / 20 (10.00%)
    2 / 20 (10.00%)
    1 / 21 (4.76%)
    2 / 20 (10.00%)
         occurrences all number
    1
    0
    1
    2
    0
    0
    2
    2
    1
    2
    Flank pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    4 / 12 (33.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    4
    0
    0
    0
    0
    0
    0
    Groin pain
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Joint stiffness
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Joint warmth
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Muscle spasms
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Muscle twitching
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Muscular weakness
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    1
    0
    0
    1
    1
    0
    0
    0
    0
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    Myalgia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    4 / 20 (20.00%)
    2 / 21 (9.52%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    4
    2
    0
    Neck pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 12 (16.67%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    2 / 20 (10.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    2
    0
    1
    0
    0
    2
    0
    0
    1
    Infections and infestations
    Abscess
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    Cellulitis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Conjunctivitis
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    0
    1
    0
    Diarrhoea infectious
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Helicobacter infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Infection
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Influenza
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    0
    1
    0
    Otitis media
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Peritonitis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Pneumonia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    2 / 12 (16.67%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    3 / 20 (15.00%)
         occurrences all number
    0
    0
    0
    2
    1
    0
    1
    1
    0
    3
    Pyuria
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    2 / 13 (15.38%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    Respiratory tract infection
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    2 / 12 (16.67%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    6
    0
    0
    2
    0
    0
    0
    0
    0
    0
    Skin infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    2 / 20 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    2
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    2 / 11 (18.18%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    2
    0
    0
    0
    0
    2
    0
    0
    0
    1
    Urinary tract infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    2 / 6 (33.33%)
    1 / 11 (9.09%)
    2 / 20 (10.00%)
    1 / 20 (5.00%)
    2 / 21 (9.52%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    1
    2
    1
    2
    0
    Viral skin infection
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    3 / 6 (50.00%)
    4 / 12 (33.33%)
    1 / 13 (7.69%)
    7 / 12 (58.33%)
    0 / 6 (0.00%)
    4 / 11 (36.36%)
    3 / 20 (15.00%)
    7 / 20 (35.00%)
    1 / 21 (4.76%)
    4 / 20 (20.00%)
         occurrences all number
    3
    5
    1
    7
    0
    6
    3
    7
    1
    4
    Dehydration
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 12 (8.33%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    1 / 20 (5.00%)
    1 / 20 (5.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    1
    1
    1
    0
    Hyperkalaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 12 (16.67%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    0
    0
    1
    1
    0
    Hypermagnesaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Hyperuricaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    0
    1
    0
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 12 (16.67%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    2 / 6 (33.33%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    2 / 20 (10.00%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
         occurrences all number
    1
    2
    1
    0
    2
    0
    0
    2
    1
    1
    Hypocalcaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 12 (16.67%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    1
    1
    0
    Hypokalaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    2 / 13 (15.38%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
         occurrences all number
    0
    0
    2
    0
    0
    1
    0
    0
    1
    2
    Hypomagnesaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hyponatraemia
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 12 (16.67%)
    1 / 13 (7.69%)
    1 / 12 (8.33%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    3 / 20 (15.00%)
    2 / 21 (9.52%)
    1 / 20 (5.00%)
         occurrences all number
    3
    2
    1
    1
    1
    0
    0
    3
    2
    1
    Hypophagia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    Hypophosphataemia
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 12 (8.33%)
    4 / 13 (30.77%)
    1 / 12 (8.33%)
    2 / 6 (33.33%)
    1 / 11 (9.09%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
         occurrences all number
    1
    1
    4
    1
    2
    1
    0
    1
    1
    1
    Vitamin D deficiency
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 12 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Jul 2016
    Amendment 01 - The main reason for this amendment was to add more specific guidance for dose modifications and to revise definitions for (DLTs), following HA feed-back.
    07 Feb 2017
    Amendment 02 - The main reasons for this amendment were to make changes requested by the HA, to prepare the protocol for inclusion of Japanese patients and to update safety monitoring. Furthermore, clarifications and correction of typos have been made to the protocol.
    14 Feb 2018
    Amendment 03 - The main purpose for this amendment was to: 1. Increase the number of pancreatic cancer patients to be enrolled in the Phase II part of the study from 20 to 40 2. Change the primary endpoint for antitumor activity in pancreatic cancer from ORR to CBR 3. Add the assessment of cfDNA as a complementary method to evaluate tumor mutational burden 4. Mention that statins should be used with caution.
    20 Jul 2018
    Amendment 04 - The main purpose for this amendment was to allow exploration of an additional, lower dose of MCS110 in patients with pancreatic cancer. Data generated in the dose escalation part of the study show preliminary signals of efficacy (1 PR, 2 SD >1 year) at the lowest dose level of MCS110 (1 mg/kg, Q3W) in combination with PDR001 in pancreatic cancer patients. In order to further explore this, 2 additional groups, each consisting of up to 20 patients with PDAC may be enrolled at either 1 mg/kg Q3W or the RP2D (7.5mg/kg, Q3W) of MCS110 in combination with PDR001 (300 mg, Q3W) respectively. Recruitment into these 2 groups was contingent upon evidence of clinical benefit in the first 20 PDAC patients treated at the RP2D.
    23 Jul 2019
    Amendment 05 - This protocol amendment revised the definition of end of study to include the option for patients still on study treatment and who, in the opinion of the investigator, were still deriving clinical benefit at the time of end of study, to transfer to another study to continue providing study treatment to these patients or to an alternative treatment option.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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