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    Clinical Trial Results:
    A Phase 2 Study of Cabiralizumab (BMS-986227, FPA008) Administered in Combination with Nivolumab (BMS-936558) with and without Chemotherapy in Patients with Advanced Pancreatic Cancer

    Summary
    EudraCT number
    		 2018-000339-28
    Trial protocol
    		 GB   ES   DK   DE   IT  
    Global end of trial date
    01 Jun 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 Jun 2024
    First version publication date
    15 Jun 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CA025-006
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03336216
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bristol-Myers Squibb
    Sponsor organisation address
    Chaussée de la Hulpe 185, Brussels, Belgium, 1170
    Public contact
    EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com
    Scientific contact
    Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    06 Sep 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    01 Jun 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Jun 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the PFS of cabiralizumab administered in combination with nivolumab with and without chemotherapy relative to investigator’s choice of chemotherapy in participants with advanced/metastatic pancreatic cancer who progressed on or after the first line of chemotherapy (either gemcitabine-based or 5-FU-based chemotherapy).
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    18 Dec 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 6
    Country: Number of subjects enrolled
    Denmark: 3
    Country: Number of subjects enrolled
    Germany: 8
    Country: Number of subjects enrolled
    Italy: 12
    Country: Number of subjects enrolled
    Japan: 13
    Country: Number of subjects enrolled
    Korea, Republic of: 7
    Country: Number of subjects enrolled
    Spain: 9
    Country: Number of subjects enrolled
    Switzerland: 4
    Country: Number of subjects enrolled
    Taiwan: 7
    Country: Number of subjects enrolled
    United Kingdom: 1
    Country: Number of subjects enrolled
    United States: 135
    Worldwide total number of subjects
    205
    EEA total number of subjects
    32
    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)
    112
    From 65 to 84 years
    92
    85 years and over
    1

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 205 participants were randomized, 179 were treated.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Arm A: Investigator Choice
    Arm description
    		 Participants receive Investigator choice of chemotherapy: 1) gemcitabine + nab-paclitaxel 2) 5-Fluorouracil/Leucovorin/Irinotecan Liposome
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1000 mg/m^2

    Investigational medicinal product name
    Nab-paclitaxel
    Investigational medicinal product code
    Other name
    ABRAXANE
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    125 mg/m^2

    Investigational medicinal product name
    Irinotecan Hydrochloride
    Investigational medicinal product code
    Other name
    FOLFIRI
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    180 mg/m^2

    Investigational medicinal product name
    Leucovorin
    Investigational medicinal product code
    Other name
    calcium folinate
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    400 mg/m^2

    Investigational medicinal product name
    Irinotecan Liposome Solution
    Investigational medicinal product code
    Other name
    ONIVYDE
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    70 mg/m^2 over 90 minutes

    Investigational medicinal product name
    5-fluorouracil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    400 mg/m^2 bolus and 2400 mg/m^2

    Arm title
    		 Arm B: Cabiralizumab + Nivolumab
    Arm description
    		 Participants receive Cabiralizumab 4MG/KG Q2W + Nivolumab 480 MG Q4W/
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    BMS-936558
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    480 mg

    Investigational medicinal product name
    Cabiralizumab
    Investigational medicinal product code
    Other name
    BMS-986227
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    4 mg/kg

    Arm title
    		 Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo
    Arm description
    		 Participants receive Cabiralizumab 4MG/KG Q2W + Nivolumab 480 MG Q4W and Gemcitabine + Nab-paclitaxel D1, 8, and 15 Q4W.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cabiralizumab
    Investigational medicinal product code
    Other name
    BMS-986227
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    4 mg/kg

    Investigational medicinal product name
    Nab-paclitaxel
    Investigational medicinal product code
    Other name
    ABRAXANE
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    125 mg/m^2

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1000 mg/m^2

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    BMS-936558
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    480 mg

    Arm title
    		 Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Arm description
    		 Participants receive Cabiralizumab 4MG/KG Q2W + Nivolumab 480 MG Q4W and Oxaliplatin/5-Fluorouracil/Leucovorin Q2W
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    BMS-936558
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    480 mg

    Investigational medicinal product name
    Cabiralizumab
    Investigational medicinal product code
    Other name
    BMS-986227
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    4 mg/kg

    Investigational medicinal product name
    Oxaliplatin
    Investigational medicinal product code
    Other name
    FOLFOX
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    85 mg/m^2

    Investigational medicinal product name
    5-fluorouracil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    400 mg/m^2 bolus and 2400 mg/m^2

    Investigational medicinal product name
    Leucovorin
    Investigational medicinal product code
    Other name
    calcium folinate
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    400 mg/m^2

    Number of subjects in period 1
    		Arm A: Investigator Choice Arm B: Cabiralizumab + Nivolumab Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Started
    54
    54
    54
    43
    Completed
    40
    49
    48
    42
    Not completed
    14
    5
    6
    1
         Participant withdrew consent
    9
    1
    -
    -
         Adverse event, non-fatal
    1
    1
    -
    -
         Not reported
    2
    -
    1
    -
         Participant no longer meets study criteria
    -
    2
    4
    1
         Other reasons
    1
    1
    1
    -
         Lost to follow-up
    1
    -
    -
    -
    Period 2
    Period 2 title
    Treatment
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Arm A: Investigator Choice
    Arm description
    		 Participants receive Investigator choice of chemotherapy: 1) gemcitabine + nab-paclitaxel 2) 5-Fluorouracil/Leucovorin/Irinotecan Liposome
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1000 mg/m^2

    Investigational medicinal product name
    Nab-paclitaxel
    Investigational medicinal product code
    Other name
    ABRAXANE
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    125 mg/m^2

    Investigational medicinal product name
    5-fluorouracil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    400 mg/m^2 bolus and 2400 mg/m^2

    Investigational medicinal product name
    Leucovorin
    Investigational medicinal product code
    Other name
    calcium folinate
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    400 mg/m^2

    Investigational medicinal product name
    Irinotecan Liposome Solution
    Investigational medicinal product code
    Other name
    ONIVYDE
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    70 mg/m^2 over 90 minutes

    Investigational medicinal product name
    Irinotecan Hydrochloride
    Investigational medicinal product code
    Other name
    FOLFIRI
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    180 mg/m^2

    Arm title
    		 Arm B: Cabiralizumab + Nivolumab
    Arm description
    		 Participants receive Cabiralizumab 4MG/KG Q2W + Nivolumab 480 MG Q4W/
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    BMS-936558
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    480 mg

    Investigational medicinal product name
    Cabiralizumab
    Investigational medicinal product code
    Other name
    BMS-986227
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    4 mg/kg

    Arm title
    		 Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo
    Arm description
    		 Participants receive Cabiralizumab 4MG/KG Q2W + Nivolumab 480 MG Q4W and Gemcitabine + Nab-paclitaxel D1, 8, and 15 Q4W.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cabiralizumab
    Investigational medicinal product code
    Other name
    BMS-986227
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    4 mg/kg

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    BMS-936558
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    480 mg

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1000 mg/m^2

    Investigational medicinal product name
    Nab-paclitaxel
    Investigational medicinal product code
    Other name
    ABRAXANE
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    125 mg/m^2

    Arm title
    		 Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Arm description
    		 Participants receive Cabiralizumab 4MG/KG Q2W + Nivolumab 480 MG Q4W and Oxaliplatin/5-Fluorouracil/Leucovorin Q2W
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    BMS-936558
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    480 mg

    Investigational medicinal product name
    Cabiralizumab
    Investigational medicinal product code
    Other name
    BMS-986227
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    4 mg/kg

    Investigational medicinal product name
    Leucovorin
    Investigational medicinal product code
    Other name
    calcium folinate
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    400 mg/m^2

    Investigational medicinal product name
    5-fluorouracil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    400 mg/m^2 bolus and 2400 mg/m^2

    Investigational medicinal product name
    Oxaliplatin
    Investigational medicinal product code
    Other name
    FOLFOX
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    85 mg/m^2

    Number of subjects in period 2
    		Arm A: Investigator Choice Arm B: Cabiralizumab + Nivolumab Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Started
    40
    49
    48
    42
    Completed
    0
    1
    0
    1
    Not completed
    40
    48
    48
    41
         Participant request to discontinue treatment
    2
    1
    2
    2
         Adverse event, serious fatal
    2
    3
    3
    4
         Disease progression
    23
    34
    33
    26
         Adverse Event unrelated to study drug
    1
    1
    1
    -
         Participant withdrew consent
    7
    2
    3
    2
         Adverse event, non-fatal
    2
    3
    4
    4
         Study drug toxicity
    -
    3
    2
    -
         Participant no longer meets study criteria
    -
    1
    -
    -
         Disease Recurrence
    1
    -
    -
    -
         Other reasons
    2
    -
    -
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Arm A: Investigator Choice
    Reporting group description
    		 Participants receive Investigator choice of chemotherapy: 1) gemcitabine + nab-paclitaxel 2) 5-Fluorouracil/Leucovorin/Irinotecan Liposome

    Reporting group title
    Arm B: Cabiralizumab + Nivolumab
    Reporting group description
    		 Participants receive Cabiralizumab 4MG/KG Q2W + Nivolumab 480 MG Q4W/

    Reporting group title
    Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo
    Reporting group description
    		 Participants receive Cabiralizumab 4MG/KG Q2W + Nivolumab 480 MG Q4W and Gemcitabine + Nab-paclitaxel D1, 8, and 15 Q4W.

    Reporting group title
    Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Reporting group description
    		 Participants receive Cabiralizumab 4MG/KG Q2W + Nivolumab 480 MG Q4W and Oxaliplatin/5-Fluorouracil/Leucovorin Q2W

    Reporting group values
    		 Arm A: Investigator Choice Arm B: Cabiralizumab + Nivolumab Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo Total
    Number of subjects
    		 54 54 54 43 205
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 31 25 37 19 112
        From 65-84 years
    		 23 29 17 23 92
        85 years and over
    		 0 0 0 1 1
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 62.7 ( 8.6 ) 64.2 ( 9.1 ) 59.1 ( 9.7 ) 64.2 ( 9.6 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 26 28 26 26 106
        Male
    		 28 26 28 17 99
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 5 0 1 0 6
        Not Hispanic or Latino
    		 46 48 45 41 180
        Unknown or Not Reported
    		 3 6 8 2 19
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0
        Asian
    		 6 8 8 12 34
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0
        Black or African American
    		 5 3 1 3 12
        White
    		 40 43 45 27 155
        More than one race
    		 0 0 0 0 0
        Unknown or Not Reported
    		 3 0 0 1 4

    End points

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    End points reporting groups
    Reporting group title
    Arm A: Investigator Choice
    Reporting group description
    		 Participants receive Investigator choice of chemotherapy: 1) gemcitabine + nab-paclitaxel 2) 5-Fluorouracil/Leucovorin/Irinotecan Liposome

    Reporting group title
    Arm B: Cabiralizumab + Nivolumab
    Reporting group description
    		 Participants receive Cabiralizumab 4MG/KG Q2W + Nivolumab 480 MG Q4W/

    Reporting group title
    Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo
    Reporting group description
    		 Participants receive Cabiralizumab 4MG/KG Q2W + Nivolumab 480 MG Q4W and Gemcitabine + Nab-paclitaxel D1, 8, and 15 Q4W.

    Reporting group title
    Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Reporting group description
    		 Participants receive Cabiralizumab 4MG/KG Q2W + Nivolumab 480 MG Q4W and Oxaliplatin/5-Fluorouracil/Leucovorin Q2W
    Reporting group title
    Arm A: Investigator Choice
    Reporting group description
    		 Participants receive Investigator choice of chemotherapy: 1) gemcitabine + nab-paclitaxel 2) 5-Fluorouracil/Leucovorin/Irinotecan Liposome

    Reporting group title
    Arm B: Cabiralizumab + Nivolumab
    Reporting group description
    		 Participants receive Cabiralizumab 4MG/KG Q2W + Nivolumab 480 MG Q4W/

    Reporting group title
    Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo
    Reporting group description
    		 Participants receive Cabiralizumab 4MG/KG Q2W + Nivolumab 480 MG Q4W and Gemcitabine + Nab-paclitaxel D1, 8, and 15 Q4W.

    Reporting group title
    Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Reporting group description
    		 Participants receive Cabiralizumab 4MG/KG Q2W + Nivolumab 480 MG Q4W and Oxaliplatin/5-Fluorouracil/Leucovorin Q2W

    Primary: Progression Free Survival (PFS) by BICR

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    End point title
    		 Progression Free Survival (PFS) by BICR
    End point description
    PFS for a participant is defined as the time from randomization date to the date of first objectively documented disease progression by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. Based on Kaplan-Meier Estimates. Analyzed for all randomized participants with at least one dose of study drug. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
    End point type
    Primary
    End point timeframe
    From randomization date to the date of first objectively documented disease progression or death (up to approximately 65 months)
    End point values
    		 Arm A: Investigator Choice Arm B: Cabiralizumab + Nivolumab Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Number of subjects analysed
    40
    49
    48
    42
    Units: Months
        median (confidence interval 95%)
    3.52 (2.53 to 4.21)
    1.92 (1.77 to 2.14)
    3.68 (1.94 to 4.83)
    3.22 (2.04 to 3.94)
    Statistical analysis title
    		 Hazard Ratio (Arm A vs B)
    Comparison groups
    Arm A: Investigator Choice v Arm B: Cabiralizumab + Nivolumab
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.47
    Confidence interval
         level
    		 60%
         sides
    2-sided
         lower limit
    		 1.19
         upper limit
    		 1.82
    Statistical analysis title
    		 Hazard Ratio (Arm A vs D)
    Comparison groups
    Arm A: Investigator Choice v Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.78
    Confidence interval
         level
    		 60%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 1.03
    Statistical analysis title
    		 Hazard Ratio (Arm A vs C)
    Comparison groups
    Arm A: Investigator Choice v Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1
    Confidence interval
         level
    		 60%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 1.3

    Secondary: Progression Free Survival Rate (PFSR) by BICR

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    End point title
    		 Progression Free Survival Rate (PFSR) by BICR
    End point description
    Progression Free Survival Rates at 6, 9, and 12 months is defined as the percentage of participants who achieve PFS at 6, 9, and 12 months. PFS for a participant is defined as the time from randomization date to the date of first objectively documented disease progression by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. Based on Kaplan-Meier Estimates. Analyzed for all randomized participants with at least one dose of study drug. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: 99999 = Data not calculable (insufficient number of participants with events)
    End point type
    Secondary
    End point timeframe
    At 6, 9, and 12 months
    End point values
    		 Arm A: Investigator Choice Arm B: Cabiralizumab + Nivolumab Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Number of subjects analysed
    40
    49
    48
    42
    Units: Percentage of participants
    number (confidence interval 95%)
        6-MONTH
    15.5 (4.8 to 31.8)
    13.1 (5.3 to 24.4)
    21.7 (10.5 to 35.4)
    17.7 (7.8 to 30.8)
        9-MONTH
    5.2 (0.4 to 20.3)
    6.5 (1.7 to 16.1)
    9.5 (2.6 to 21.8)
    10.1 (3.2 to 21.7)
        12-MONTH
    99999 (99999 to 99999)
    2.2 (0.2 to 10.0)
    3.2 (0.3 to 13.6)
    5.1 (0.9 to 15.0)
    No statistical analyses for this end point

    Secondary: Progression Free Survival (PFS) by Investigator

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    End point title
    		 Progression Free Survival (PFS) by Investigator
    End point description
    PFS for a participant is defined as the time from randomization date to the date of first objectively documented disease progression by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. Based on Kaplan-Meier Estimates. Analyzed for all randomized participants with at least one dose of study drug. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
    End point type
    Secondary
    End point timeframe
    From randomization date to the date of first objectively documented disease progression or death (up to approximately 65 months)
    End point values
    		 Arm A: Investigator Choice Arm B: Cabiralizumab + Nivolumab Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Number of subjects analysed
    40
    49
    48
    42
    Units: Months
        median (confidence interval 95%)
    3.38 (1.97 to 3.98)
    1.81 (1.74 to 1.97)
    3.68 (2.00 to 4.17)
    2.92 (1.81 to 3.94)
    Statistical analysis title
    		 Hazard Ratio (Arm A vs B)
    Comparison groups
    Arm A: Investigator Choice v Arm B: Cabiralizumab + Nivolumab
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.64
    Confidence interval
         level
    		 60%
         sides
    2-sided
         lower limit
    		 1.33
         upper limit
    		 2.02
    Statistical analysis title
    		 Hazard Ratio (Arm A vs D)
    Comparison groups
    Arm A: Investigator Choice v Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.72
    Confidence interval
         level
    		 60%
         sides
    2-sided
         lower limit
    		 0.55
         upper limit
    		 0.94
    Statistical analysis title
    		 Hazard Ratio (Arm A vs C)
    Comparison groups
    Arm A: Investigator Choice v Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.13
    Confidence interval
         level
    		 60%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.46

    Secondary: Progression Free Survival Rate (PFSR) by Investigator

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    End point title
    		 Progression Free Survival Rate (PFSR) by Investigator
    End point description
    Progression Free Survival Rates at 6, 9, and 12 months is defined as the percentage of participants who achieve PFS at 6, 9, and 12 months. PFS for a participant is defined as the time from randomization date to the date of first objectively documented disease progression by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. Based on Kaplan-Meier Estimates. Analyzed for all randomized participants with at least one dose of study drug. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: 99999 = Data not available (minimum follow up not reached).
    End point type
    Secondary
    End point timeframe
    At 6, 9, and 12 months
    End point values
    		 Arm A: Investigator Choice Arm B: Cabiralizumab + Nivolumab Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Number of subjects analysed
    40
    49
    48
    42
    Units: Percentage of participants
    number (confidence interval 95%)
        6-MONTH
    14.9 (4.9 to 30.0)
    16.3 (7.6 to 27.9)
    17.6 (8.2 to 29.8)
    14.7 (6.0 to 27.1)
        9-MONTH
    11.2 (3.0 to 25.6)
    8.2 (2.6 to 17.9)
    5.0 (0.9 to 14.7)
    7.3 (1.97 to 17.9)
        12-MONTH
    3.7 (0.3 to 15.9)
    99999 (99999 to 99999)
    2.5 (0.2 to 11.2)
    4.9 (0.9 to 14.5)
    No statistical analyses for this end point

    Secondary: Objective Response Rate (ORR) by BICR

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    End point title
    		 Objective Response Rate (ORR) by BICR
    End point description
    ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method. Analyzed for all randomized participants with at least one dose of study drug. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
    End point type
    Secondary
    End point timeframe
    From randomization to the date of objectively documented progression per RECIST v1.1 or the date of subsequent anti-cancer therapy, whichever occurs first (up to approximately 65 months)
    End point values
    		 Arm A: Investigator Choice Arm B: Cabiralizumab + Nivolumab Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Number of subjects analysed
    40
    49
    48
    42
    Units: Percentage of participants
        number (confidence interval 95%)
    2.5 (0.1 to 13.2)
    4.1 (0.5 to 14.0)
    12.5 (4.7 to 25.2)
    9.5 (2.7 to 22.6)
    Statistical analysis title
    		 DIFFERENCE OF ORR (Arm A vs B)
    Comparison groups
    Arm A: Investigator Choice v Arm B: Cabiralizumab + Nivolumab
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6537 [1]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Strata adjusted difference
    Point estimate
    1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.5
         upper limit
    		 9
    Notes
    [1] - Stratified CMH test stratified by ECOG and prior chemotherapy
    Statistical analysis title
    		 DIFFERENCE OF ORR (Arm A vs D)
    Comparison groups
    Arm A: Investigator Choice v Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5171 [2]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Strata adjusted difference
    Point estimate
    5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8
         upper limit
    		 18.1
    Notes
    [2] - Stratified CMH test stratified by ECOG and prior chemotherapy
    Statistical analysis title
    		 DIFFERENCE OF ORR (Arm A vs C)
    Comparison groups
    Arm A: Investigator Choice v Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0951 [3]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Strata adjusted difference
    Point estimate
    12.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.1
         upper limit
    		 21.9
    Notes
    [3] - Stratified CMH test stratified by ECOG and prior chemotherapy

    Secondary: Objective Response Rate (ORR) by Investigator

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    End point title
    		 Objective Response Rate (ORR) by Investigator
    End point description
    ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method. Analyzed for all randomized participants with at least one dose of study drug. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
    End point type
    Secondary
    End point timeframe
    From randomization to the date of objectively documented progression per RECIST v1.1 or the date of subsequent anti-cancer therapy, whichever occurs first (up to approximately 65 months)
    End point values
    		 Arm A: Investigator Choice Arm B: Cabiralizumab + Nivolumab Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Number of subjects analysed
    40
    49
    48
    42
    Units: Percentage of participants
        number (confidence interval 95%)
    5.0 (0.6 to 16.9)
    4.1 (0.5 to 14.0)
    6.3 (1.3 to 17.2)
    4.8 (0.6 to 16.2)
    Statistical analysis title
    		 DIFFERENCE OF ORR (Arm A vs B)
    Comparison groups
    Arm A: Investigator Choice v Arm B: Cabiralizumab + Nivolumab
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8505 [4]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Strata adjusted difference
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.4
         upper limit
    		 7.7
    Notes
    [4] - Stratified CMH test stratified by ECOG and prior chemotherapy
    Statistical analysis title
    		 DIFFERENCE OF ORR (Arm A vs D)
    Comparison groups
    Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo v Arm A: Investigator Choice
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9087 [5]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Strata adjusted difference
    Point estimate
    0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.7
         upper limit
    		 12.1
    Notes
    [5] - Stratified CMH test stratified by ECOG and prior chemotherapy
    Statistical analysis title
    		 DIFFERENCE OF ORR (Arm A vs C)
    Comparison groups
    Arm A: Investigator Choice v Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8144 [6]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Strata adjusted difference
    Point estimate
    1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.9
         upper limit
    		 12.8
    Notes
    [6] - Stratified CMH test stratified by ECOG and prior chemotherapy

    Secondary: Duration of Response (DOR) by BICR

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    End point title
    		 Duration of Response (DOR) by BICR
    End point description
    DOR is defined as the time between the date of first response and the date of the first objectively documented tumor progression by BICR per RECIST v1.1 or death, whichever occurs first. Estimated using Kaplan-Meier method. Analyzed for all randomized participants (with at least one dose of study drug) with CR or PR. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: 99999 = Data not calculable (insufficient number of participants with events)
    End point type
    Secondary
    End point timeframe
    From randomization the date of the first objectively documented tumor progression or death, whichever occurs first (up to approximately 65 months)
    End point values
    		 Arm A: Investigator Choice Arm B: Cabiralizumab + Nivolumab Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Number of subjects analysed
    1
    2
    6
    4
    Units: Months
        median (confidence interval 95%)
    99999 (99999 to 99999)
    4.2 (3.9 to 99999)
    4.6 (3.0 to 99999)
    99999 (5.6 to 99999)
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR) by Investigator

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    End point title
    		 Duration of Response (DOR) by Investigator
    End point description
    DOR is defined as the time between the date of first response and the date of the first objectively documented tumor progression by investigator per RECIST v1.1 or death, whichever occurs first. Estimated using Kaplan-Meier method. Analyzed for all randomized participants (with at least one dose of study drug) with CR or PR. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: 99999 = Data not calculable (insufficient number of participants with events)
    End point type
    Secondary
    End point timeframe
    From randomization the date of the first objectively documented tumor progression or death, whichever occurs first (up to approximately 65 months)
    End point values
    		 Arm A: Investigator Choice Arm B: Cabiralizumab + Nivolumab Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Number of subjects analysed
    2
    2
    3
    2
    Units: Months
        median (confidence interval 95%)
    10.2 (2.7 to 99999)
    7.3 (4.5 to 99999)
    99999 (3.7 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Overall Survival Rates (OSR)

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    End point title
    		 Overall Survival Rates (OSR)
    End point description
    Overall survival at 6 months, 1 year, and 2 years is defined as the percentage of participants who are alive at 6 months, 1 year, and 2 years. Based on Kaplan-Meier Estimates. Analyzed for all randomized participants with at least one dose of study drug. Note: 99999 = Data estimable (minimum follow up not reached)
    End point type
    Secondary
    End point timeframe
    At 6 months, 1 year, and 2 years
    End point values
    		 Arm A: Investigator Choice Arm B: Cabiralizumab + Nivolumab Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Number of subjects analysed
    40
    49
    48
    42
    Units: Percentage of participants
    number (confidence interval 95%)
        6-MONTH
    55.8 (38.8 to 69.8)
    40.1 (26.1 to 53.8)
    54.2 (39.2 to 67.0)
    44.8 (29.4 to 59.0)
        12-MONTH
    14.7 (5.4 to 28.3)
    20.1 (10.0 to 32.7)
    20.6 (10.6 to 33.0)
    17.4 (7.7 to 30.4)
        24-MONTH
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    OS is defined as the time from randomization to the date of death due to any cause. Based on Kaplan-Meier Estimates. Analyzed for all randomized participants with at least one dose of study drug.
    End point type
    Secondary
    End point timeframe
    From randomization to the date of death to any cause (up to approximately 65 months)
    End point values
    		 Arm A: Investigator Choice Arm B: Cabiralizumab + Nivolumab Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Number of subjects analysed
    40
    49
    48
    42
    Units: Months
        median (confidence interval 95%)
    6.28 (4.53 to 8.11)
    4.44 (3.19 to 7.26)
    6.72 (4.96 to 8.54)
    5.68 (4.57 to 7.33)
    Statistical analysis title
    		 Hazard Ratio (Arm A vs B)
    Comparison groups
    Arm A: Investigator Choice v Arm B: Cabiralizumab + Nivolumab
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Cox proportional hazard
    Point estimate
    1.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 1.96
    Statistical analysis title
    		 Hazard Ratio (Arm A vs D)
    Comparison groups
    Arm A: Investigator Choice v Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.45
         upper limit
    		 1.46
    Statistical analysis title
    		 Hazard Ratio (Arm A vs C)
    Comparison groups
    Arm A: Investigator Choice v Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Cox proportional hazard
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.59
         upper limit
    		 1.86

    Secondary: The Number of Participants with Adverse Events (AEs)

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    End point title
    		 The Number of Participants with Adverse Events (AEs)
    End point description
    An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Analyzed for all treated participants.
    End point type
    Secondary
    End point timeframe
    From first dose to 100 days after last dose of study therapy (up to approximately 51 months)
    End point values
    		 Arm A: Investigator Choice Arm B: Cabiralizumab + Nivolumab Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Number of subjects analysed
    40
    49
    48
    42
    Units: Participants
    40
    49
    48
    42
    No statistical analyses for this end point

    Secondary: The Number of Participants with Serious Adverse Events (SAEs)

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    End point title
    		 The Number of Participants with Serious Adverse Events (SAEs)
    End point description
    A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. Analyzed for all treated participants.
    End point type
    Secondary
    End point timeframe
    From first dose to 100 days after last dose of study therapy (up to approximately 51 months)
    End point values
    		 Arm A: Investigator Choice Arm B: Cabiralizumab + Nivolumab Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Number of subjects analysed
    40
    49
    48
    42
    Units: Participants
    23
    41
    39
    33
    No statistical analyses for this end point

    Secondary: The Number of Participants who Experienced Abnormal Hepatic Tests

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    End point title
    		 The Number of Participants who Experienced Abnormal Hepatic Tests
    End point description
    The number of treated participants who experienced a laboratory abnormality of the liver during the course of the study. Analyzed for all treated participants with at least one on-treatment hepatic measurement. Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN)
    End point type
    Secondary
    End point timeframe
    From first dose and 100 days after last dose of study therapy (up to approximately 51 months)
    End point values
    		 Arm A: Investigator Choice Arm B: Cabiralizumab + Nivolumab Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Number of subjects analysed
    38
    45
    45
    41
    Units: Participants
        ALT or AST > 3xULN
    2
    21
    37
    34
        ALT or AST > 5xULN
    0
    10
    19
    18
        ALT or AST > 10xULN
    0
    2
    6
    2
        ALT or AST > 12xULN
    0
    2
    4
    2
        ALT or AST > 20xULN
    0
    1
    1
    1
        TOTAL BILIRUBIN (=B) > 2xULN
    3
    3
    2
    5
        ALP > 1.5xULN
    27
    31
    35
    30
        ALT/AST > 3xULN; =B > 2xULN + ALP <=2ULN/ 3 DAYS
    0
    1
    1
    1
    No statistical analyses for this end point

    Secondary: The Number of Participants with Adverse Events (AEs) Leading to Discontinuation

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    End point title
    		 The Number of Participants with Adverse Events (AEs) Leading to Discontinuation
    End point description
    An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Analyzed for all treated participants.
    End point type
    Secondary
    End point timeframe
    From first dose to 100 days after last dose of study therapy (up to approximately 51 months)
    End point values
    		 Arm A: Investigator Choice Arm B: Cabiralizumab + Nivolumab Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Number of subjects analysed
    40
    49
    48
    42
    Units: Participants
    6
    11
    11
    8
    No statistical analyses for this end point

    Secondary: The Number of Participants who Died

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    End point title
    		 The Number of Participants who Died
    End point description
    The number of participants that died during the study. Analyzed for all treated participants.
    End point type
    Secondary
    End point timeframe
    From first dose to 150 days after last dose of study therapy (up to approximately 53 months)
    End point values
    		 Arm A: Investigator Choice Arm B: Cabiralizumab + Nivolumab Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Number of subjects analysed
    40
    49
    48
    42
    Units: Participants
    25
    33
    30
    28
    No statistical analyses for this end point

    Secondary: The Number of Participants with On-Treatment Laboratory Abnormalities in Specific Thyroid Tests

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    End point title
    		 The Number of Participants with On-Treatment Laboratory Abnormalities in Specific Thyroid Tests
    End point description
    The number of treated participants who experienced a laboratory abnormality of the thyroid during the course of the study. Analyzed for all treated participants with at least one on-treatment thyroid stimulating hormone (TSH) measurement. Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN) Upper Limit of Normal (ULN)
    End point type
    Secondary
    End point timeframe
    From first dose and 100 days after last dose of study therapy (up to approximately 51 months)
    End point values
    		 Arm A: Investigator Choice Arm B: Cabiralizumab + Nivolumab Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Number of subjects analysed
    11
    23
    25
    20
    Units: Participants
        TSH > ULN
    3
    4
    10
    6
        TSH > ULN WITH TSH <= ULN AT BASELINE
    0
    2
    4
    2
        TSH > ULN WITH AT LEAST ONE T3/T4 TEST VALUE < LLN
    0
    1
    1
    0
        TSH > ULN WITH ALL T3/T4 TEST VALUES >= LLN
    0
    0
    0
    0
        TSH > ULN WITH T3/T4 TEST MISSING
    0
    1
    0
    0
        TSH < LLN
    0
    0
    1
    1
        TSH < LLN WITH TSH >= LLN AT BASELINE
    0
    0
    0
    1
        TSH < LLN WITH AT LEAST ONE T3/T4 TEST VALUE > ULN
    0
    0
    0
    0
        TSH < LLN WITH ALL OTHER T3/T4 TEST VALUES <= ULN
    0
    0
    0
    0
        TSH < LLN WITH T3/T4 TEST MISSING
    0
    0
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All-cause mortality was assessed from a participants first dose to their study completion (up to approximately 65 months). SAEs and NSAEs were assessed from first dose to 100 days following last dose (up to approximately 51 months)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Arm A1: Investigator Choice - Gem/Nab-Based Chemo
    Reporting group description
    		 Participants receive Investigator choice of chemotherapy: - gemcitabine + nab-paclitaxel

    Reporting group title
    Arm A2: Investigator Choice - 5 FU-Based Chemo
    Reporting group description
    		 Participants receive Investigator choice of chemotherapy: - 5-Fluorouracil/Leucovorin/Irinotecan Liposome

    Reporting group title
    Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo
    Reporting group description
    		 Participants receive Cabiralizumab 4MG/KG Q2W + Nivolumab 480 MG Q4W and Oxaliplatin/5-Fluorouracil/Leucovorin Q2W.

    Reporting group title
    Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo
    Reporting group description
    		 Participants receive Cabiralizumab 4MG/KG Q2W + Nivolumab 480 MG Q4W and Gemcitabine + Nab-paclitaxel D1, 8, and 15 Q4W.

    Reporting group title
    Arm B: Cabiralizumab + Nivolumab
    Reporting group description
    		 Participants receive Cabiralizumab 4MG/KG Q2W + Nivolumab 480 MG Q4W.

    Serious adverse events
    		 Arm A1: Investigator Choice - Gem/Nab-Based Chemo Arm A2: Investigator Choice - 5 FU-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm B: Cabiralizumab + Nivolumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    11 / 21 (52.38%)
    12 / 19 (63.16%)
    33 / 42 (78.57%)
    39 / 48 (81.25%)
    41 / 49 (83.67%)
         number of deaths (all causes)
    19
    17
    39
    46
    46
         number of deaths resulting from adverse events
    9
    6
    20
    23
    29
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to central nervous system
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Adenocarcinoma gastric
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Malignant neoplasm progression
         subjects affected / exposed
    8 / 21 (38.10%)
    6 / 19 (31.58%)
    15 / 42 (35.71%)
    19 / 48 (39.58%)
    22 / 49 (44.90%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 6
    0 / 15
    0 / 19
    0 / 22
         deaths causally related to treatment / all
    0 / 8
    0 / 6
    0 / 15
    0 / 19
    0 / 22
    Metastatic neoplasm
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Oncologic complication
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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 / 1
    Vascular disorders
    Embolism
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Capillary leak syndrome
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Haematoma
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Hypovolaemic shock
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    General disorders and administration site conditions
    Face oedema
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Death
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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 / 1
    Asthenia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    General physical health deterioration
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Oedema peripheral
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Pain
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    3 / 49 (6.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Pyrexia
         subjects affected / exposed
    1 / 21 (4.76%)
    2 / 19 (10.53%)
    5 / 42 (11.90%)
    3 / 48 (6.25%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    0 / 6
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    2 / 42 (4.76%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Pneumonitis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    1 / 42 (2.38%)
    4 / 48 (8.33%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
    4 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    2 / 42 (4.76%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Psychotic disorder
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Mental status changes
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Liver function test increased
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood electrolytes abnormal
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Troponin increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Fall
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    2 / 49 (4.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Spinal compression fracture
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Myocardial infarction
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Cardiac arrest
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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 / 1
    Myocarditis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Nervous system disorders
    Neurotoxicity
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Metabolic encephalopathy
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Ischaemic stroke
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Dizziness
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Cerebral ischaemia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Seizure
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Syncope
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Transient ischaemic attack
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Bone marrow failure
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    2 / 42 (4.76%)
    2 / 48 (4.17%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Neutropenia
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    2 / 42 (4.76%)
    1 / 48 (2.08%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Abdominal pain
         subjects affected / exposed
    2 / 21 (9.52%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    3 / 48 (6.25%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal distension
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Constipation
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Diarrhoea
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 19 (10.53%)
    1 / 42 (2.38%)
    2 / 48 (4.17%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Gastric haemorrhage
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Large intestinal stenosis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Ileus
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Haematemesis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    3 / 48 (6.25%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Large intestinal obstruction
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Stomatitis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Small intestinal haemorrhage
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Rectal haemorrhage
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Pancreatitis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Obstruction gastric
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Nausea
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Subileus
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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 / 1
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    2 / 48 (4.17%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 19 (10.53%)
    1 / 42 (2.38%)
    1 / 48 (2.08%)
    3 / 49 (6.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    1 / 1
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Acute hepatic failure
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Hepatic failure
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Cholecystitis acute
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Cholangitis
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 19 (0.00%)
    2 / 42 (4.76%)
    0 / 48 (0.00%)
    2 / 49 (4.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Biliary obstruction
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Portal hypertension
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Jaundice cholestatic
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Immune-mediated hepatitis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    3 / 42 (7.14%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    3 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stevens-Johnson syndrome
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    2 / 42 (4.76%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    4 / 48 (8.33%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 1
    Haematuria
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Musculoskeletal and connective tissue disorders
    Muscular weakness
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Spinal pain
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Pathological fracture
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Myositis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    1 / 48 (2.08%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bacterial infection
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Bacteraemia
         subjects affected / exposed
    2 / 21 (9.52%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    2 / 48 (4.17%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Biliary tract infection
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Device related infection
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Encephalitis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Klebsiella bacteraemia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Infection
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Fungal infection
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Escherichia bacteraemia
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Influenza
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Klebsiella sepsis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Liver abscess
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    1 / 48 (2.08%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Oral candidiasis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Pneumonia
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    3 / 48 (6.25%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Sepsis
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 19 (0.00%)
    6 / 42 (14.29%)
    4 / 48 (8.33%)
    3 / 49 (6.12%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    2 / 6
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 19 (10.53%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Spontaneous bacterial peritonitis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Urinary tract infection
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Dehydration
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 19 (5.26%)
    1 / 42 (2.38%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemic hyperosmolar nonketotic syndrome
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Hyperglycaemia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    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
    Failure to thrive
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    1 / 48 (2.08%)
    2 / 49 (4.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Diabetes mellitus inadequate control
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Hyponatraemia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    2 / 49 (4.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypophosphataemia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Arm A1: Investigator Choice - Gem/Nab-Based Chemo Arm A2: Investigator Choice - 5 FU-Based Chemo Arm D: Cabiralizumab + Nivolumab + 5-FU-Based Chemo Arm C: Cabiralizumab + Nivolumab + Gemcitabine-Based Chemo Arm B: Cabiralizumab + Nivolumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    19 / 21 (90.48%)
    17 / 19 (89.47%)
    41 / 42 (97.62%)
    47 / 48 (97.92%)
    46 / 49 (93.88%)
    Vascular disorders
    Hot flush
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    0
    1
    1
    Deep vein thrombosis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    2 / 42 (4.76%)
    2 / 48 (4.17%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    2
    2
    1
    Thrombophlebitis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Hypertension
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    6 / 42 (14.29%)
    8 / 48 (16.67%)
    8 / 49 (16.33%)
         occurrences all number
    0
    1
    7
    8
    13
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    3 / 21 (14.29%)
    1 / 19 (5.26%)
    5 / 42 (11.90%)
    5 / 48 (10.42%)
    3 / 49 (6.12%)
         occurrences all number
    3
    3
    8
    7
    3
    Catheter site phlebitis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Chills
         subjects affected / exposed
    5 / 21 (23.81%)
    2 / 19 (10.53%)
    6 / 42 (14.29%)
    8 / 48 (16.67%)
    2 / 49 (4.08%)
         occurrences all number
    6
    3
    8
    9
    2
    Face oedema
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    13 / 42 (30.95%)
    5 / 48 (10.42%)
    3 / 49 (6.12%)
         occurrences all number
    0
    0
    14
    7
    3
    Facial pain
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Fatigue
         subjects affected / exposed
    10 / 21 (47.62%)
    10 / 19 (52.63%)
    23 / 42 (54.76%)
    29 / 48 (60.42%)
    25 / 49 (51.02%)
         occurrences all number
    13
    14
    28
    36
    25
    Influenza like illness
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    5 / 48 (10.42%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    8
    1
    Mucosal inflammation
         subjects affected / exposed
    2 / 21 (9.52%)
    2 / 19 (10.53%)
    7 / 42 (16.67%)
    7 / 48 (14.58%)
    0 / 49 (0.00%)
         occurrences all number
    2
    2
    11
    7
    0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    1
    0
    0
    1
    Oedema peripheral
         subjects affected / exposed
    4 / 21 (19.05%)
    0 / 19 (0.00%)
    6 / 42 (14.29%)
    15 / 48 (31.25%)
    4 / 49 (8.16%)
         occurrences all number
    4
    0
    6
    16
    4
    Pain
         subjects affected / exposed
    3 / 21 (14.29%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    2 / 48 (4.17%)
    4 / 49 (8.16%)
         occurrences all number
    4
    0
    1
    2
    4
    Peripheral swelling
         subjects affected / exposed
    2 / 21 (9.52%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    1 / 48 (2.08%)
    1 / 49 (2.04%)
         occurrences all number
    2
    0
    1
    1
    1
    Pyrexia
         subjects affected / exposed
    6 / 21 (28.57%)
    3 / 19 (15.79%)
    15 / 42 (35.71%)
    18 / 48 (37.50%)
    12 / 49 (24.49%)
         occurrences all number
    11
    9
    23
    25
    16
    Temperature intolerance
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    3 / 42 (7.14%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    4
    0
    1
    Generalised oedema
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    3 / 42 (7.14%)
    5 / 48 (10.42%)
    0 / 49 (0.00%)
         occurrences all number
    0
    0
    3
    5
    0
    Reproductive system and breast disorders
    Pelvic pain
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    2 / 48 (4.17%)
    0 / 49 (0.00%)
         occurrences all number
    1
    1
    0
    2
    0
    Vulvovaginal dryness
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Vaginal discharge
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    4 / 21 (19.05%)
    1 / 19 (5.26%)
    7 / 42 (16.67%)
    5 / 48 (10.42%)
    0 / 49 (0.00%)
         occurrences all number
    4
    1
    7
    7
    0
    Dyspnoea
         subjects affected / exposed
    4 / 21 (19.05%)
    2 / 19 (10.53%)
    6 / 42 (14.29%)
    9 / 48 (18.75%)
    3 / 49 (6.12%)
         occurrences all number
    5
    2
    6
    9
    3
    Cough
         subjects affected / exposed
    2 / 21 (9.52%)
    2 / 19 (10.53%)
    7 / 42 (16.67%)
    8 / 48 (16.67%)
    3 / 49 (6.12%)
         occurrences all number
    2
    2
    7
    10
    3
    Hiccups
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 19 (10.53%)
    2 / 42 (4.76%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    3
    3
    0
    1
    Wheezing
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    1 / 42 (2.38%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    Pulmonary embolism
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 19 (10.53%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    1 / 49 (2.04%)
         occurrences all number
    0
    2
    0
    1
    1
    Pneumonitis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    2 / 42 (4.76%)
    3 / 48 (6.25%)
    4 / 49 (8.16%)
         occurrences all number
    0
    0
    2
    3
    4
    Pleural effusion
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    2
    Nasal congestion
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 19 (5.26%)
    2 / 42 (4.76%)
    1 / 48 (2.08%)
    1 / 49 (2.04%)
         occurrences all number
    1
    1
    2
    1
    1
    Hypoxia
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    2 / 21 (9.52%)
    1 / 19 (5.26%)
    2 / 42 (4.76%)
    2 / 48 (4.17%)
    1 / 49 (2.04%)
         occurrences all number
    2
    1
    2
    2
    1
    Depression
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    3 / 42 (7.14%)
    6 / 48 (12.50%)
    3 / 49 (6.12%)
         occurrences all number
    0
    0
    3
    6
    3
    Insomnia
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 19 (5.26%)
    6 / 42 (14.29%)
    3 / 48 (6.25%)
    7 / 49 (14.29%)
         occurrences all number
    1
    1
    6
    3
    8
    Somnambulism
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 19 (0.00%)
    23 / 42 (54.76%)
    18 / 48 (37.50%)
    15 / 49 (30.61%)
         occurrences all number
    1
    0
    27
    27
    17
    Alanine aminotransferase decreased
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 19 (0.00%)
    16 / 42 (38.10%)
    18 / 48 (37.50%)
    9 / 49 (18.37%)
         occurrences all number
    1
    0
    22
    29
    9
    Amylase increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    4 / 48 (8.33%)
    0 / 49 (0.00%)
         occurrences all number
    0
    0
    1
    4
    0
    Aspartate aminotransferase decreased
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 21 (14.29%)
    1 / 19 (5.26%)
    24 / 42 (57.14%)
    27 / 48 (56.25%)
    14 / 49 (28.57%)
         occurrences all number
    4
    3
    26
    38
    15
    Blood alkaline phosphatase increased
         subjects affected / exposed
    2 / 21 (9.52%)
    1 / 19 (5.26%)
    10 / 42 (23.81%)
    14 / 48 (29.17%)
    9 / 49 (18.37%)
         occurrences all number
    2
    3
    11
    21
    9
    Blood bilirubin increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    3 / 42 (7.14%)
    3 / 48 (6.25%)
    5 / 49 (10.20%)
         occurrences all number
    0
    0
    3
    4
    7
    Blood creatinine increased
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    2 / 48 (4.17%)
    4 / 49 (8.16%)
         occurrences all number
    1
    0
    1
    2
    5
    Brain natriuretic peptide increased
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    International normalised ratio increased
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    1 / 42 (2.38%)
    2 / 48 (4.17%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    2
    3
    0
    Lymphocyte count decreased
         subjects affected / exposed
    1 / 21 (4.76%)
    3 / 19 (15.79%)
    7 / 42 (16.67%)
    6 / 48 (12.50%)
    4 / 49 (8.16%)
         occurrences all number
    3
    3
    10
    7
    4
    Neutrophil count decreased
         subjects affected / exposed
    7 / 21 (33.33%)
    4 / 19 (21.05%)
    9 / 42 (21.43%)
    6 / 48 (12.50%)
    1 / 49 (2.04%)
         occurrences all number
    15
    6
    15
    7
    1
    Neutrophil count increased
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    Platelet count decreased
         subjects affected / exposed
    7 / 21 (33.33%)
    3 / 19 (15.79%)
    8 / 42 (19.05%)
    18 / 48 (37.50%)
    1 / 49 (2.04%)
         occurrences all number
    20
    5
    14
    42
    1
    Weight decreased
         subjects affected / exposed
    3 / 21 (14.29%)
    2 / 19 (10.53%)
    4 / 42 (9.52%)
    7 / 48 (14.58%)
    5 / 49 (10.20%)
         occurrences all number
    3
    2
    4
    7
    5
    White blood cell count decreased
         subjects affected / exposed
    4 / 21 (19.05%)
    3 / 19 (15.79%)
    6 / 42 (14.29%)
    11 / 48 (22.92%)
    2 / 49 (4.08%)
         occurrences all number
    10
    4
    13
    13
    4
    White blood cell count increased
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    10 / 42 (23.81%)
    8 / 48 (16.67%)
    7 / 49 (14.29%)
         occurrences all number
    0
    0
    11
    9
    7
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 19 (0.00%)
    2 / 42 (4.76%)
    3 / 48 (6.25%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    2
    3
    2
    Fall
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 19 (0.00%)
    4 / 42 (9.52%)
    5 / 48 (10.42%)
    2 / 49 (4.08%)
         occurrences all number
    1
    0
    5
    6
    3
    Infusion related reaction
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    3 / 42 (7.14%)
    1 / 48 (2.08%)
    4 / 49 (8.16%)
         occurrences all number
    0
    0
    7
    2
    4
    Procedural pain
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Cardiac disorders
    Cardiac failure congestive
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Tachycardia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    3 / 48 (6.25%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    1
    3
    1
    Nervous system disorders
    Balance disorder
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    0
    0
    1
    Peripheral sensory neuropathy
         subjects affected / exposed
    2 / 21 (9.52%)
    0 / 19 (0.00%)
    9 / 42 (21.43%)
    6 / 48 (12.50%)
    0 / 49 (0.00%)
         occurrences all number
    2
    0
    9
    6
    0
    Headache
         subjects affected / exposed
    1 / 21 (4.76%)
    3 / 19 (15.79%)
    4 / 42 (9.52%)
    5 / 48 (10.42%)
    6 / 49 (12.24%)
         occurrences all number
    2
    9
    5
    5
    7
    Dysgeusia
         subjects affected / exposed
    1 / 21 (4.76%)
    2 / 19 (10.53%)
    8 / 42 (19.05%)
    4 / 48 (8.33%)
    4 / 49 (8.16%)
         occurrences all number
    1
    2
    8
    4
    4
    Dizziness
         subjects affected / exposed
    4 / 21 (19.05%)
    2 / 19 (10.53%)
    7 / 42 (16.67%)
    6 / 48 (12.50%)
    3 / 49 (6.12%)
         occurrences all number
    5
    2
    7
    7
    3
    Polyneuropathy
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    0
    1
    1
    Post herpetic neuralgia
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Presyncope
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Neuropathy peripheral
         subjects affected / exposed
    6 / 21 (28.57%)
    1 / 19 (5.26%)
    7 / 42 (16.67%)
    13 / 48 (27.08%)
    0 / 49 (0.00%)
         occurrences all number
    6
    1
    8
    14
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    9 / 21 (42.86%)
    5 / 19 (26.32%)
    17 / 42 (40.48%)
    34 / 48 (70.83%)
    13 / 49 (26.53%)
         occurrences all number
    18
    8
    18
    63
    16
    Leukopenia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    3 / 48 (6.25%)
    0 / 49 (0.00%)
         occurrences all number
    0
    0
    1
    6
    0
    Lymphopenia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    3 / 48 (6.25%)
    0 / 49 (0.00%)
         occurrences all number
    0
    0
    1
    4
    0
    Thrombocytopenia
         subjects affected / exposed
    4 / 21 (19.05%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    19 / 48 (39.58%)
    0 / 49 (0.00%)
         occurrences all number
    6
    0
    0
    34
    0
    Neutropenia
         subjects affected / exposed
    2 / 21 (9.52%)
    0 / 19 (0.00%)
    6 / 42 (14.29%)
    13 / 48 (27.08%)
    0 / 49 (0.00%)
         occurrences all number
    2
    0
    10
    20
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    Eye disorders
    Periorbital oedema
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    16 / 42 (38.10%)
    21 / 48 (43.75%)
    13 / 49 (26.53%)
         occurrences all number
    0
    0
    18
    25
    13
    Vision blurred
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    3 / 42 (7.14%)
    4 / 48 (8.33%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    3
    4
    1
    Visual impairment
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Vitreous floaters
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Halo vision
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Gastrointestinal disorders
    Enteritis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Abdominal distension
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    2 / 42 (4.76%)
    0 / 48 (0.00%)
    5 / 49 (10.20%)
         occurrences all number
    0
    0
    2
    0
    6
    Abdominal pain
         subjects affected / exposed
    6 / 21 (28.57%)
    4 / 19 (21.05%)
    9 / 42 (21.43%)
    7 / 48 (14.58%)
    15 / 49 (30.61%)
         occurrences all number
    6
    7
    11
    12
    16
    Abdominal pain upper
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 19 (5.26%)
    6 / 42 (14.29%)
    1 / 48 (2.08%)
    2 / 49 (4.08%)
         occurrences all number
    1
    1
    6
    1
    2
    Ascites
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    4 / 48 (8.33%)
    4 / 49 (8.16%)
         occurrences all number
    0
    0
    1
    4
    4
    Constipation
         subjects affected / exposed
    7 / 21 (33.33%)
    8 / 19 (42.11%)
    12 / 42 (28.57%)
    13 / 48 (27.08%)
    13 / 49 (26.53%)
         occurrences all number
    7
    10
    16
    15
    16
    Defaecation urgency
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 19 (10.53%)
    0 / 42 (0.00%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences all number
    0
    2
    0
    1
    0
    Diarrhoea
         subjects affected / exposed
    5 / 21 (23.81%)
    9 / 19 (47.37%)
    24 / 42 (57.14%)
    16 / 48 (33.33%)
    11 / 49 (22.45%)
         occurrences all number
    6
    14
    40
    23
    18
    Dry mouth
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    8 / 42 (19.05%)
    4 / 48 (8.33%)
    5 / 49 (10.20%)
         occurrences all number
    0
    0
    8
    4
    5
    Dyspepsia
         subjects affected / exposed
    2 / 21 (9.52%)
    0 / 19 (0.00%)
    3 / 42 (7.14%)
    2 / 48 (4.17%)
    6 / 49 (12.24%)
         occurrences all number
    2
    0
    3
    2
    6
    Haematochezia
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    2 / 48 (4.17%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    0
    2
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    2 / 42 (4.76%)
    3 / 48 (6.25%)
    4 / 49 (8.16%)
         occurrences all number
    0
    0
    2
    3
    4
    Lip dry
         subjects affected / exposed
    2 / 21 (9.52%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Mouth ulceration
         subjects affected / exposed
    2 / 21 (9.52%)
    1 / 19 (5.26%)
    1 / 42 (2.38%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences all number
    2
    1
    2
    4
    0
    Nausea
         subjects affected / exposed
    7 / 21 (33.33%)
    9 / 19 (47.37%)
    23 / 42 (54.76%)
    16 / 48 (33.33%)
    19 / 49 (38.78%)
         occurrences all number
    7
    11
    32
    20
    25
    Rectal haemorrhage
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    1 / 42 (2.38%)
    2 / 48 (4.17%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    1
    2
    0
    Small intestinal haemorrhage
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Stomatitis
         subjects affected / exposed
    5 / 21 (23.81%)
    2 / 19 (10.53%)
    13 / 42 (30.95%)
    7 / 48 (14.58%)
    4 / 49 (8.16%)
         occurrences all number
    7
    3
    16
    11
    5
    Vomiting
         subjects affected / exposed
    9 / 21 (42.86%)
    7 / 19 (36.84%)
    13 / 42 (30.95%)
    15 / 48 (31.25%)
    11 / 49 (22.45%)
         occurrences all number
    11
    9
    18
    18
    17
    Flatulence
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 19 (5.26%)
    1 / 42 (2.38%)
    1 / 48 (2.08%)
    2 / 49 (4.08%)
         occurrences all number
    1
    1
    1
    1
    2
    Haemorrhoids
         subjects affected / exposed
    3 / 21 (14.29%)
    1 / 19 (5.26%)
    2 / 42 (4.76%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences all number
    3
    1
    2
    1
    0
    Hepatobiliary disorders
    Biliary obstruction
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Hepatic function abnormal
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    Portal vein thrombosis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Nail discolouration
         subjects affected / exposed
    2 / 21 (9.52%)
    0 / 19 (0.00%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    0
    0
    2
    Dry skin
         subjects affected / exposed
    2 / 21 (9.52%)
    3 / 19 (15.79%)
    3 / 42 (7.14%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    2
    3
    3
    0
    1
    Alopecia
         subjects affected / exposed
    9 / 21 (42.86%)
    2 / 19 (10.53%)
    0 / 42 (0.00%)
    13 / 48 (27.08%)
    5 / 49 (10.20%)
         occurrences all number
    9
    2
    0
    14
    5
    Skin hyperpigmentation
         subjects affected / exposed
    2 / 21 (9.52%)
    1 / 19 (5.26%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    2
    1
    1
    0
    0
    Skin burning sensation
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Rash
         subjects affected / exposed
    4 / 21 (19.05%)
    1 / 19 (5.26%)
    14 / 42 (33.33%)
    14 / 48 (29.17%)
    11 / 49 (22.45%)
         occurrences all number
    6
    1
    17
    16
    13
    Pruritus
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 19 (5.26%)
    6 / 42 (14.29%)
    12 / 48 (25.00%)
    8 / 49 (16.33%)
         occurrences all number
    1
    1
    7
    15
    11
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 19 (10.53%)
    4 / 42 (9.52%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences all number
    0
    2
    4
    1
    0
    Rash maculo-papular
         subjects affected / exposed
    2 / 21 (9.52%)
    0 / 19 (0.00%)
    5 / 42 (11.90%)
    11 / 48 (22.92%)
    7 / 49 (14.29%)
         occurrences all number
    2
    0
    6
    15
    8
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    2 / 42 (4.76%)
    4 / 48 (8.33%)
    0 / 49 (0.00%)
         occurrences all number
    0
    0
    2
    5
    0
    Proteinuria
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    4 / 48 (8.33%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    1
    4
    1
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    5 / 48 (10.42%)
    2 / 49 (4.08%)
         occurrences all number
    1
    0
    1
    6
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 21 (4.76%)
    2 / 19 (10.53%)
    6 / 42 (14.29%)
    6 / 48 (12.50%)
    4 / 49 (8.16%)
         occurrences all number
    1
    2
    6
    13
    4
    Back pain
         subjects affected / exposed
    2 / 21 (9.52%)
    3 / 19 (15.79%)
    3 / 42 (7.14%)
    5 / 48 (10.42%)
    9 / 49 (18.37%)
         occurrences all number
    2
    3
    3
    6
    10
    Bone pain
         subjects affected / exposed
    2 / 21 (9.52%)
    1 / 19 (5.26%)
    1 / 42 (2.38%)
    1 / 48 (2.08%)
    0 / 49 (0.00%)
         occurrences all number
    2
    3
    1
    1
    0
    Muscle spasms
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    1 / 42 (2.38%)
    2 / 48 (4.17%)
    1 / 49 (2.04%)
         occurrences all number
    0
    2
    1
    2
    1
    Muscular weakness
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 19 (5.26%)
    2 / 42 (4.76%)
    5 / 48 (10.42%)
    1 / 49 (2.04%)
         occurrences all number
    1
    1
    2
    5
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    2 / 42 (4.76%)
    0 / 48 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    2
    0
    1
    Myalgia
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 19 (5.26%)
    5 / 42 (11.90%)
    5 / 48 (10.42%)
    2 / 49 (4.08%)
         occurrences all number
    1
    2
    7
    11
    2
    Pain in extremity
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 19 (5.26%)
    1 / 42 (2.38%)
    5 / 48 (10.42%)
    2 / 49 (4.08%)
         occurrences all number
    1
    1
    1
    6
    3
    Pain in jaw
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    1 / 42 (2.38%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    Infections and infestations
    Candida infection
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 19 (0.00%)
    1 / 42 (2.38%)
    4 / 48 (8.33%)
    2 / 49 (4.08%)
         occurrences all number
    0
    0
    1
    5
    2
    Biliary tract infection
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Endocarditis staphylococcal
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    2 / 21 (9.52%)
    0 / 19 (0.00%)
    3 / 42 (7.14%)
    3 / 48 (6.25%)
    5 / 49 (10.20%)
         occurrences all number
    3
    0
    3
    4
    5
    Skin infection
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Metabolism and nutrition disorders
    Hypocalcaemia
         subjects affected / exposed
    1 / 21 (4.76%)
    2 / 19 (10.53%)
    8 / 42 (19.05%)
    6 / 48 (12.50%)
    2 / 49 (4.08%)
         occurrences all number
    2
    2
    8
    7
    2
    Decreased appetite
         subjects affected / exposed
    7 / 21 (33.33%)
    6 / 19 (31.58%)
    23 / 42 (54.76%)
    17 / 48 (35.42%)
    11 / 49 (22.45%)
         occurrences all number
    9
    7
    31
    19
    11
    Dehydration
         subjects affected / exposed
    2 / 21 (9.52%)
    2 / 19 (10.53%)
    7 / 42 (16.67%)
    4 / 48 (8.33%)
    9 / 49 (18.37%)
         occurrences all number
    3
    2
    12
    5
    12
    Hyperglycaemia
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 19 (5.26%)
    4 / 42 (9.52%)
    7 / 48 (14.58%)
    2 / 49 (4.08%)
         occurrences all number
    2
    1
    4
    8
    2
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 21 (4.76%)
    3 / 19 (15.79%)
    5 / 42 (11.90%)
    7 / 48 (14.58%)
    3 / 49 (6.12%)
         occurrences all number
    2
    4
    7
    10
    3
    Hypokalaemia
         subjects affected / exposed
    1 / 21 (4.76%)
    8 / 19 (42.11%)
    6 / 42 (14.29%)
    9 / 48 (18.75%)
    8 / 49 (16.33%)
         occurrences all number
    1
    11
    8
    15
    10
    Hypomagnesaemia
         subjects affected / exposed
    1 / 21 (4.76%)
    2 / 19 (10.53%)
    2 / 42 (4.76%)
    3 / 48 (6.25%)
    4 / 49 (8.16%)
         occurrences all number
    1
    2
    2
    3
    12
    Hyponatraemia
         subjects affected / exposed
    1 / 21 (4.76%)
    2 / 19 (10.53%)
    11 / 42 (26.19%)
    3 / 48 (6.25%)
    7 / 49 (14.29%)
         occurrences all number
    1
    2
    15
    7
    14
    Hypophosphataemia
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 19 (10.53%)
    11 / 42 (26.19%)
    9 / 48 (18.75%)
    5 / 49 (10.20%)
         occurrences all number
    0
    2
    12
    12
    5
    Vitamin D deficiency
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 19 (5.26%)
    0 / 42 (0.00%)
    0 / 48 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 Nov 2017
    1) Expanded rationale for combining immunotherapy and chemotherapy agents 2) Removed criteria excluding participants who had any GI surgery and an inability to tolerate oral medication 3) Added criteria for permanent dose discontinuation and exceptions 4)Added Cycle 2 and Cycle 3 168 hour post dose time point PK collection for cabiralizumab and nivolumab
    24 Feb 2018
    1) Removal the cross over post disease progression for participants treated with chemotherapy only. 2) Patient-reported outcomes added to on-treatment, safety follow-up and long term follow-up assessments. 3) Additional data added to support the combination of cabiralizumab and nivolumab.
    09 Mar 2018
    1) Updated eligible participants 2) All participants must have fresh tumor biopsy taken during screening. 3) Added analysis of anti-tumor activity in the gut microbiome 4) Patient-reported outcomes added to on-treatment assessments 5) If ONIVYDE-based regimen is not available per institution/country guidelines, FOLFIRI can be used in Arm A. 6) Adequate organ function is defined as ALT and AST < 2 x ULN
    17 Jun 2019
    1) Clarified that BICR will be used to assess the primary endpoint of PFS per RECIST v1.1. 2) Clarified the assessment (Investigator/BICR) used for each efficacy evaluation included as a secondary endpoint. 3) Time of on-treatment biopsy was changed to an earlier time point on Cycle 2 Day 8.

    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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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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