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    Clinical Trial Results:
    An open-label, Phase II, platform trial evaluating safety and efficacy of multiple ezabenlimab anti-PD-1 based combination regimens in PD-(L)1 naïve and PD-(L)1 pretreated patient populations with advanced and/or metastatic solid tumours who have had at least one line of systemic therapy

    Summary
    EudraCT number
    		 2018-002344-81
    Trial protocol
    		 GB  
    Global end of trial date
    03 Dec 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 Dec 2025
    First version publication date
    19 Dec 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    1381-0009
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03697304
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Boehringer Ingelheim
    Sponsor organisation address
    Binger Strasse 173, Ingelheim am Rhein, Germany, 55216
    Public contact
    Boehringer Ingelheim, Call Center, Boehringer Ingelheim, 001 18002430127, clintriage.rdg@boehringer-ingelheim.com
    Scientific contact
    Boehringer Ingelheim, Call Center, Boehringer Ingelheim, 001 18002430127, clintriage.rdg@boehringer-ingelheim.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
    17 Apr 2025
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    03 Dec 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Dec 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this research trial was to evaluate patient clinical response to ezabenlimab (BI 754091) in combination with combination partners presented in individual Modules.
    Protection of trial subjects
    Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. If a subject continued to take trial medication, close monitoring was adhered to and all adverse events recorded. Rules were implemented in all trials whereby doses would be reduced if required. Thereafter, if further events were reported, the subject would be withdrawn from the trial. Symptomatic treatment of tumor associated symptoms were allowed throughout.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    19 Mar 2019
    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: 23
    Country: Number of subjects enrolled
    United Kingdom: 64
    Country: Number of subjects enrolled
    United States: 236
    Worldwide total number of subjects
    323
    EEA total number of subjects
    0
    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)
    163
    From 65 to 84 years
    151
    85 years and over
    9

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Platform trial evaluating the safety and efficacy of different ezabenlimab (BI 754091) treatment regimens on patients with different types of advanced/metastatic tumors: module C evaluated ezabenlimab in combination with BI 836880, and module A evaluated ezabenlimab in combination with BI 754111.

    Pre-assignment
    Screening details
    		 All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    This trial was conducted open-label in both treatment modules.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Module C, Cohort 1: GEC patients
    Arm description
    		 Patients with locally advanced, unresectable or metastatic gastric adenocarcinoma or gastro-oesophageal adenocarcinoma (GEC) with at least one prior systemic treatment, who failed standard therapy, for whom no further effective options existed, and with no prior PD-1 or PD-L1-based treatment, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, in the form of i.v. infusion, on Day 1 of 21-day cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BI 836880
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles.

    Investigational medicinal product name
    Ezabenlimab
    Investigational medicinal product code
    Other name
    BI 754091
    Pharmaceutical forms
    Concentrate for solution for infusion, Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles.

    Arm title
    		 Module C, Cohort 2: 2ary resistance patients
    Arm description
    		 Patients with any advanced or metastatic solid tumor (excluding non-squamous lung cancer, non-small-cell lung cancer, and melanoma) who had received prior anti-PD-1- or anti-PD-L1-based treatment and progressed after achieving benefit (at least stable disease with a minimum duration of benefit of 4 months) and minimum treatment duration of 2 months on the previous anti-PD-1- or anti-PD-L1-based treatment without progressive disease, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880 on Day 1, intravenously, on Day1 of 21-day cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BI 836880
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles.

    Investigational medicinal product name
    Ezabenlimab
    Investigational medicinal product code
    Other name
    BI 754091
    Pharmaceutical forms
    Concentrate for solution for infusion, Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles.

    Arm title
    		 Module C, Cohort 3: 1ary resistance patients
    Arm description
    		 Patients with select advanced or metastatic solid tumors with prior anti-PD-1- or anti-PD-L1-based treatment without achieving benefit ( stable disease duration of less than 4 months or progressive disease in less than 4 months while on treatment), were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BI 836880
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles.

    Investigational medicinal product name
    Ezabenlimab
    Investigational medicinal product code
    Other name
    BI 754091
    Pharmaceutical forms
    Solution for infusion, Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles.

    Arm title
    		 Module C, Cohort 4: CRC patients
    Arm description
    		 Patients with locally advanced, unresectable or metastatic second-line or greater, microsatellite-stable colorectal cancer (CRC) without prior anti-PD-1- or anti-PD-L1-based treatment, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ezabenlimab
    Investigational medicinal product code
    Other name
    BI 754091
    Pharmaceutical forms
    Concentrate for solution for infusion, Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles.

    Investigational medicinal product name
    BI 836880
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles.

    Arm title
    		 Module C, Cohort 5: EC patients
    Arm description
    		 Patients with advanced endometrial carcinoma (EC), excluding microsatellite instability-high or mismatch repair deficient types, who progressed following one line of chemotherapy, were not eligible for curative surgery or radiation, and had not been previously treated with anti-PD-1- or anti-PD-L1-based therapies, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BI 836880
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles.

    Investigational medicinal product name
    Ezabenlimab
    Investigational medicinal product code
    Other name
    BI 754091
    Pharmaceutical forms
    Concentrate for solution for infusion, Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles.

    Arm title
    		 Module A, Cohort 1: GEC patients
    Arm description
    		 Patients with locally advanced, unresectable or metastatic gastric adenocarcinoma or gastro-oesophageal adenocarcinoma, who received prior anti-PD-1 or anti-PD-L1-based treatment, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BI 754111
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles.

    Investigational medicinal product name
    Ezabenlimab
    Investigational medicinal product code
    Other name
    BI 754091
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles.

    Arm title
    		 Module A, Cohort 2: 2ary resistance patients
    Arm description
    		 Patients with any advanced or metastatic solid tumors who had been previously treated with anti-PD-1 or anti-PD-L1-based therapies, and who progressed after achieving benefit (at least stable disease with a minimum duration of benefit of 6 months) and minimum treatment duration of 2 months without experiencing disease progression, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BI 754111
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles.

    Investigational medicinal product name
    Ezabenlimab
    Investigational medicinal product code
    Other name
    BI 754091
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles.

    Arm title
    		 Module A, Cohort 3: 1ary resistance patients
    Arm description
    		 Patients with select advanced or metastatic solid tumor types, who have been previously treated with previous anti-PD-1 or anti-PD-L1-based therapies without achieving benefit (stable disease for less than 6 months or progressive disease in less than 6 months), were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ezabenlimab
    Investigational medicinal product code
    Other name
    BI 754091
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles.

    Investigational medicinal product name
    BI 754111
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles.

    Number of subjects in period 1 [1]
    		Module C, Cohort 1: GEC patients Module C, Cohort 2: 2ary resistance patients Module C, Cohort 3: 1ary resistance patients Module C, Cohort 4: CRC patients Module C, Cohort 5: EC patients Module A, Cohort 1: GEC patients Module A, Cohort 2: 2ary resistance patients Module A, Cohort 3: 1ary resistance patients
    Started
    28
    30
    28
    30
    18
    2
    33
    42
    Completed
    0
    0
    0
    0
    0
    0
    0
    0
    Not completed
    28
    30
    28
    30
    18
    2
    33
    42
         Adverse event, serious fatal
    1
    2
    4
    -
    1
    -
    1
    -
         Physician decision
    -
    2
    -
    -
    -
    -
    1
    1
         Consent withdrawal
    1
    2
    -
    4
    4
    -
    1
    1
         Adverse event, non-fatal
    4
    4
    2
    4
    4
    1
    5
    3
         Progressive disease
    21
    20
    22
    22
    8
    1
    25
    37
         Other than listed
    1
    -
    -
    -
    1
    -
    -
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: From the 323 patients screened, 211 started treatment.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Module C, Cohort 1: GEC patients
    Reporting group description
    		 Patients with locally advanced, unresectable or metastatic gastric adenocarcinoma or gastro-oesophageal adenocarcinoma (GEC) with at least one prior systemic treatment, who failed standard therapy, for whom no further effective options existed, and with no prior PD-1 or PD-L1-based treatment, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, in the form of i.v. infusion, on Day 1 of 21-day cycles.

    Reporting group title
    Module C, Cohort 2: 2ary resistance patients
    Reporting group description
    		 Patients with any advanced or metastatic solid tumor (excluding non-squamous lung cancer, non-small-cell lung cancer, and melanoma) who had received prior anti-PD-1- or anti-PD-L1-based treatment and progressed after achieving benefit (at least stable disease with a minimum duration of benefit of 4 months) and minimum treatment duration of 2 months on the previous anti-PD-1- or anti-PD-L1-based treatment without progressive disease, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880 on Day 1, intravenously, on Day1 of 21-day cycles.

    Reporting group title
    Module C, Cohort 3: 1ary resistance patients
    Reporting group description
    		 Patients with select advanced or metastatic solid tumors with prior anti-PD-1- or anti-PD-L1-based treatment without achieving benefit ( stable disease duration of less than 4 months or progressive disease in less than 4 months while on treatment), were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles.

    Reporting group title
    Module C, Cohort 4: CRC patients
    Reporting group description
    		 Patients with locally advanced, unresectable or metastatic second-line or greater, microsatellite-stable colorectal cancer (CRC) without prior anti-PD-1- or anti-PD-L1-based treatment, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles.

    Reporting group title
    Module C, Cohort 5: EC patients
    Reporting group description
    		 Patients with advanced endometrial carcinoma (EC), excluding microsatellite instability-high or mismatch repair deficient types, who progressed following one line of chemotherapy, were not eligible for curative surgery or radiation, and had not been previously treated with anti-PD-1- or anti-PD-L1-based therapies, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles.

    Reporting group title
    Module A, Cohort 1: GEC patients
    Reporting group description
    		 Patients with locally advanced, unresectable or metastatic gastric adenocarcinoma or gastro-oesophageal adenocarcinoma, who received prior anti-PD-1 or anti-PD-L1-based treatment, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles.

    Reporting group title
    Module A, Cohort 2: 2ary resistance patients
    Reporting group description
    		 Patients with any advanced or metastatic solid tumors who had been previously treated with anti-PD-1 or anti-PD-L1-based therapies, and who progressed after achieving benefit (at least stable disease with a minimum duration of benefit of 6 months) and minimum treatment duration of 2 months without experiencing disease progression, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles.

    Reporting group title
    Module A, Cohort 3: 1ary resistance patients
    Reporting group description
    		 Patients with select advanced or metastatic solid tumor types, who have been previously treated with previous anti-PD-1 or anti-PD-L1-based therapies without achieving benefit (stable disease for less than 6 months or progressive disease in less than 6 months), were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles.

    Reporting group values
    		 Module C, Cohort 1: GEC patients Module C, Cohort 2: 2ary resistance patients Module C, Cohort 3: 1ary resistance patients Module C, Cohort 4: CRC patients Module C, Cohort 5: EC patients Module A, Cohort 1: GEC patients Module A, Cohort 2: 2ary resistance patients Module A, Cohort 3: 1ary resistance patients Total
    Number of subjects
    		 28 30 28 30 18 2 33 42 211
    Age categorical
    Treated set: all patients treated with at least one dose of trial medications.
    Units: Subjects
        In utero
    		 0 0 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0 0 0 0
        Adults (18-64 years)
    		 23 14 19 20 4 1 10 18 109
        From 65-84 years
    		 5 15 8 9 14 1 22 23 97
        85 years and over
    		 0 1 1 1 0 0 1 1 5
    Age Continuous
    Treated set: all patients treated with at least one dose of trial medications.
    Units: years
        arithmetic mean (standard deviation)
    		 56.5 ( 10.7 ) 63.2 ( 13.3 ) 60.6 ( 10.9 ) 57.7 ( 13.5 ) 67.8 ( 11.3 ) 61.0 ( 14.1 ) 68.6 ( 7.2 ) 64.9 ( 10.4 ) -
    Sex: Female, Male
    Treated set: all patients treated with at least one dose of trial medications.
    Units: Participants
        Female
    		 8 10 7 13 18 1 14 22 93
        Male
    		 20 20 21 17 0 1 19 20 118
    Race/Ethnicity, Customized
    Treated set: all patients treated with at least one dose of trial medications.
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 1 0 0 1 0 2
        Asian
    		 1 2 2 2 2 0 0 1 10
        Black or African American
    		 0 0 1 1 2 0 4 2 10
        Other
    		 20 12 5 1 1 0 0 3 42
        White
    		 7 16 20 25 13 2 28 36 147
    Ethnicity (NIH/OMB)
    Treated set: all patients treated with at least one dose of trial medications.
    Units: Subjects
        Hispanic or Latino
    		 0 2 1 3 0 0 0 4 10
        Not Hispanic or Latino
    		 8 16 22 27 17 2 33 37 162
        Unknown or Not Reported
    		 20 12 5 0 1 0 0 1 39

    End points

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    End points reporting groups
    Reporting group title
    Module C, Cohort 1: GEC patients
    Reporting group description
    		 Patients with locally advanced, unresectable or metastatic gastric adenocarcinoma or gastro-oesophageal adenocarcinoma (GEC) with at least one prior systemic treatment, who failed standard therapy, for whom no further effective options existed, and with no prior PD-1 or PD-L1-based treatment, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, in the form of i.v. infusion, on Day 1 of 21-day cycles.

    Reporting group title
    Module C, Cohort 2: 2ary resistance patients
    Reporting group description
    		 Patients with any advanced or metastatic solid tumor (excluding non-squamous lung cancer, non-small-cell lung cancer, and melanoma) who had received prior anti-PD-1- or anti-PD-L1-based treatment and progressed after achieving benefit (at least stable disease with a minimum duration of benefit of 4 months) and minimum treatment duration of 2 months on the previous anti-PD-1- or anti-PD-L1-based treatment without progressive disease, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880 on Day 1, intravenously, on Day1 of 21-day cycles.

    Reporting group title
    Module C, Cohort 3: 1ary resistance patients
    Reporting group description
    		 Patients with select advanced or metastatic solid tumors with prior anti-PD-1- or anti-PD-L1-based treatment without achieving benefit ( stable disease duration of less than 4 months or progressive disease in less than 4 months while on treatment), were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles.

    Reporting group title
    Module C, Cohort 4: CRC patients
    Reporting group description
    		 Patients with locally advanced, unresectable or metastatic second-line or greater, microsatellite-stable colorectal cancer (CRC) without prior anti-PD-1- or anti-PD-L1-based treatment, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles.

    Reporting group title
    Module C, Cohort 5: EC patients
    Reporting group description
    		 Patients with advanced endometrial carcinoma (EC), excluding microsatellite instability-high or mismatch repair deficient types, who progressed following one line of chemotherapy, were not eligible for curative surgery or radiation, and had not been previously treated with anti-PD-1- or anti-PD-L1-based therapies, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles.

    Reporting group title
    Module A, Cohort 1: GEC patients
    Reporting group description
    		 Patients with locally advanced, unresectable or metastatic gastric adenocarcinoma or gastro-oesophageal adenocarcinoma, who received prior anti-PD-1 or anti-PD-L1-based treatment, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles.

    Reporting group title
    Module A, Cohort 2: 2ary resistance patients
    Reporting group description
    		 Patients with any advanced or metastatic solid tumors who had been previously treated with anti-PD-1 or anti-PD-L1-based therapies, and who progressed after achieving benefit (at least stable disease with a minimum duration of benefit of 6 months) and minimum treatment duration of 2 months without experiencing disease progression, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles.

    Reporting group title
    Module A, Cohort 3: 1ary resistance patients
    Reporting group description
    		 Patients with select advanced or metastatic solid tumor types, who have been previously treated with previous anti-PD-1 or anti-PD-L1-based therapies without achieving benefit (stable disease for less than 6 months or progressive disease in less than 6 months), were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles.

    Primary: [Module C] Objective response (OR)

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    End point title
    		 [Module C] Objective response (OR) [1] [2]
    End point description
    Confirmed objective response (OR), defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR), assessed by the investigator according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). Complete response (CR) was defined as the disappearance of all target lesions and partial response (PR) was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference. Treated set of the module C: all patients treated with at least one dose of trial medications.
    End point type
    Primary
    End point timeframe
    From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 188.3 weeks.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No further statistical analysis was defined for the primary endpoint.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed on Module C.
    End point values
    		 Module C, Cohort 1: GEC patients Module C, Cohort 2: 2ary resistance patients Module C, Cohort 3: 1ary resistance patients Module C, Cohort 4: CRC patients Module C, Cohort 5: EC patients
    Number of subjects analysed
    28
    30
    28
    30
    18
    Units: Percentage of participants
        number (confidence interval 95%)
    14.3 (4.0 to 32.7)
    23.3 (9.9 to 42.3)
    0.0 (0.0 to 12.3)
    3.3 (0.1 to 17.2)
    44.4 (21.5 to 69.2)
    No statistical analyses for this end point

    Primary: [Module C] Objective response (OR) - Bayesian hierarchical model

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    End point title
    		 [Module C] Objective response (OR) - Bayesian hierarchical model [3] [4]
    End point description
    Confirmed objective response (OR), defined as the objective response rate (ORR) of participants with best overall response of complete response (CR) or partial response (PR), assessed by the investigator according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). Complete response (CR) was defined as the disappearance of all target lesions and partial response (PR) was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference. The estimated objective response rate is presented by the posterior medians of the Bayesian hierarchical model and by the correspondent credible intervals. The median is actually the posterior median and the confidence interval is actually the credible interval. Treated set of the module C: all patients treated with at least one dose of trial medications.
    End point type
    Primary
    End point timeframe
    From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 188.3 weeks.
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No further statistical analysis was defined for the primary endpoint.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed on Module C.
    End point values
    		 Module C, Cohort 1: GEC patients Module C, Cohort 2: 2ary resistance patients Module C, Cohort 3: 1ary resistance patients Module C, Cohort 4: CRC patients Module C, Cohort 5: EC patients
    Number of subjects analysed
    28
    30
    28
    30
    18
    Units: Estimated ORR
        median (confidence interval 97.5%)
    11.95 (3.72 to 25.31)
    20.21 (9.61 to 36.1)
    2.75 (0.17 to 10.15)
    5.26 (0.83 to 14.87)
    36.13 (17.15 to 59.63)
    No statistical analyses for this end point

    Primary: [Module A] Objective response (OR)

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    End point title
    		 [Module A] Objective response (OR) [5] [6]
    End point description
    Confirmed objective response (OR), defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR), assessed by the investigator according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). Complete response (CR) was defined as the disappearance of all target lesions and partial response (PR) was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference. Treated set of the module A: all patients treated with at least one dose of trial medications.
    End point type
    Primary
    End point timeframe
    From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 152.4 weeks.
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No further statistical analysis was defined for the primary endpoint.
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed on Module A.
    End point values
    		 Module A, Cohort 1: GEC patients Module A, Cohort 2: 2ary resistance patients Module A, Cohort 3: 1ary resistance patients
    Number of subjects analysed
    2
    33
    42
    Units: Percentage of participants
        number (confidence interval 95%)
    0.0 (0.0 to 84.2)
    6.1 (0.7 to 20.2)
    9.5 (2.7 to 22.6)
    No statistical analyses for this end point

    Primary: [Module A] Objective response (OR) - Bayesian hierarchical model

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    End point title
    		 [Module A] Objective response (OR) - Bayesian hierarchical model [7] [8]
    End point description
    Confirmed objective response (OR), defined as the objective response rate (ORR) of participants with best overall response of complete response (CR) or partial response (PR), assessed by the investigator according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). Complete response (CR) was defined as the disappearance of all target lesions and partial response (PR) was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference. The estimated objective response rate is presented by the posterior medians of the Bayesian hierarchical model and by the correspondent credible intervals. The median is actually the posterior median and the confidence interval is actually the credible interval. Treated set of the module A: all patients treated with at least one dose of trial medications.
    End point type
    Primary
    End point timeframe
    From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 152.4 weeks.
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No further statistical analysis was defined for the primary endpoint.
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed on Module A.
    End point values
    		 Module A, Cohort 1: GEC patients Module A, Cohort 2: 2ary resistance patients Module A, Cohort 3: 1ary resistance patients
    Number of subjects analysed
    2
    33
    42
    Units: Estimated ORR
        median (confidence interval 97.5%)
    9.69 (0.88 to 35.04)
    8.23 (2.12 to 18.91)
    6.67 (2.3 to 16.02)
    No statistical analyses for this end point

    Secondary: [Module C] Duration of response (DoR)

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    End point title
    		 [Module C] Duration of response (DoR) [9]
    End point description
    Duration of response (DoR) was defined as the time from first documented complete response (CR) or partial response (PR) (RECIST v1.1) among patients with objective response (OR), according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). Complete response (CR) was defined as the disappearance of all target lesions and partial response (PR) was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference. DoR parameters were calculated based on Kaplan-Meier estimation. Treated set of the module C: all patients treated with at least one dose of trial medications. Only patients that had an OR were included in the analysis.
    End point type
    Secondary
    End point timeframe
    From first documented CR or PR (RECIST v1.1) until the earlier of disease progression or death. Up to 174.6 weeks.
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed on Module C.
    End point values
    		 Module C, Cohort 1: GEC patients Module C, Cohort 2: 2ary resistance patients Module C, Cohort 3: 1ary resistance patients Module C, Cohort 4: CRC patients Module C, Cohort 5: EC patients
    Number of subjects analysed
    4
    9
    2
    2
    8
    Units: Weeks
        median (full range (min-max))
    105.95 (12.3 to 174.6)
    30.90 (6.4 to 81.3)
    8.50 (8.4 to 8.6)
    25.00 (12.1 to 37.9)
    47.30 (6.1 to 143.1)
    No statistical analyses for this end point

    Secondary: [Module C] Disease control (DC)

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    End point title
    		 [Module C] Disease control (DC) [10]
    End point description
    Disease Control (DC) defined as the percentage of patients with best overall response of complete response (CR), partial response (PR), or stable disease (SD), assessed by the investigator according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). CR was defined as the disappearance of all target lesions, PR was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference, SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study, and PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. Treated set of the module C: all patients treated with at least one dose of trial medications.
    End point type
    Secondary
    End point timeframe
    From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 188.3 weeks.
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed on Module C.
    End point values
    		 Module C, Cohort 1: GEC patients Module C, Cohort 2: 2ary resistance patients Module C, Cohort 3: 1ary resistance patients Module C, Cohort 4: CRC patients Module C, Cohort 5: EC patients
    Number of subjects analysed
    28
    30
    28
    30
    18
    Units: Percentage of participants
        number (confidence interval 95%)
    57.1 (37.2 to 75.5)
    73.3 (54.1 to 87.7)
    42.9 (24.5 to 62.8)
    56.7 (37.4 to 74.5)
    77.8 (52.4 to 93.6)
    No statistical analyses for this end point

    Secondary: [Module C] Disease control (DC) - bayesian hierarchical model (BHM)

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    End point title
    		 [Module C] Disease control (DC) - bayesian hierarchical model (BHM) [11]
    End point description
    Defined as the disease control rate (DCR) of participants with best overall response of CR, PR, or stable disease (SD), assessed by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target lesions, PR as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference, SD as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study, and PD as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The estimated DCR is presented by the posterior medians of the BHM and by the correspondent credible intervals. The median is actually the posterior median and the confidence interval is actually the credible interval. Treated set of the module C: all patients treated with at least one dose of trial medications.
    End point type
    Secondary
    End point timeframe
    From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 188.3 weeks.
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed on Module C.
    End point values
    		 Module C, Cohort 1: GEC patients Module C, Cohort 2: 2ary resistance patients Module C, Cohort 3: 1ary resistance patients Module C, Cohort 4: CRC patients Module C, Cohort 5: EC patients
    Number of subjects analysed
    28
    30
    28
    30
    18
    Units: Estimated DCR
        median (confidence interval 97.5%)
    64.7 (45.4 to 77.8)
    70.4 (56.7 to 83.8)
    44.7 (29.1 to 59.8)
    57.5 (42.1 to 71.5)
    82.2 (66.7 to 96.1)
    No statistical analyses for this end point

    Secondary: [Module C] Progression-free survival (PFS)

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    End point title
    		 [Module C] Progression-free survival (PFS) [12]
    End point description
    Progression-free survival (PFS) was defined as the time from first treatment administration until progressive disease (PD), according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1), or death from any cause, whichever occurred earlier. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. PFS parameters were calculated based on Kaplan-Meier estimation. Treated set of the module C: all patients treated with at least one dose of trial medications.
    End point type
    Secondary
    End point timeframe
    From first drug administration until PD or death, whichever occurred earlier. Up to approximately 186.1 weeks.
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed on Module C.
    End point values
    		 Module C, Cohort 1: GEC patients Module C, Cohort 2: 2ary resistance patients Module C, Cohort 3: 1ary resistance patients Module C, Cohort 4: CRC patients Module C, Cohort 5: EC patients
    Number of subjects analysed
    28
    30
    28
    30
    18 [13]
    Units: Weeks
        median (confidence interval 95%)
    13.4 (6.1 to 33.7)
    29.1 (13.0 to 48.7)
    6.1 (5.7 to 12.1)
    12.6 (6.1 to 23.6)
    75.0 (24.9 to 99999)
    Notes
    [13] - 99999 = not calculable due
    No statistical analyses for this end point

    Secondary: [Module A] Disease control (DC)

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    End point title
    		 [Module A] Disease control (DC) [14]
    End point description
    Disease Control (DC) defined as the percentage of patients with best overall response of complete response (CR), partial response (PR), or stable disease (SD), assessed by the investigator according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). CR was defined as the disappearance of all target lesions, PR was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference, SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study, and PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. Treated set of the module A: all patients treated with at least one dose of trial medications.
    End point type
    Secondary
    End point timeframe
    From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 152.4 weeks.
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed on Module A.
    End point values
    		 Module A, Cohort 1: GEC patients Module A, Cohort 2: 2ary resistance patients Module A, Cohort 3: 1ary resistance patients
    Number of subjects analysed
    2
    33
    42
    Units: Percentage of participants
        number (confidence interval 95%)
    0 (0.0 to 84.2)
    42.4 (25.5 to 60.8)
    45.2 (29.8 to 61.3)
    No statistical analyses for this end point

    Secondary: [Module A] Duration of response (DoR)

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    End point title
    		 [Module A] Duration of response (DoR) [15]
    End point description
    Duration of response (DoR) was defined as the time from first documented complete response (CR) or partial response (PR) (RECIST v1.1) among patients with objective response (OR), according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). Complete response (CR) was defined as the disappearance of all target lesions and partial response (PR) was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference. DoR parameters were calculated based on Kaplan-Meier estimation. Treated set of the module A: all patients treated with at least one dose of trial medications. Only patients that had an OR were included in the analysis.
    End point type
    Secondary
    End point timeframe
    From first documented CR or PR (RECIST v1.1) until the earlier of disease progression or death. Up to 63.6 weeks.
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed on Module A.
    End point values
    		 Module A, Cohort 1: GEC patients Module A, Cohort 2: 2ary resistance patients Module A, Cohort 3: 1ary resistance patients
    Number of subjects analysed
    0 [16]
    3
    8
    Units: Weeks
        median (full range (min-max))
    ( to )
    12.30 (5.7 to 31.4)
    28.30 (0.1 to 63.6)
    Notes
    [16] - No patient had OR in this cohort.
    No statistical analyses for this end point

    Secondary: [Module A] Disease control (DC) - bayesian hierarchical model

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    End point title
    		 [Module A] Disease control (DC) - bayesian hierarchical model [17]
    End point description
    Defined as the disease control rate (DCR) of participants with best overall response of CR, PR, or stable disease (SD), assessed by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target lesions, PR as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference, SD as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study, and PD as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The estimated DCR is presented by the posterior medians of the BHM and by the correspondent credible intervals. The median is actually the posterior median and the confidence interval is actually the credible interval. Treated set of the module A: all patients treated with at least one dose of trial medications.
    End point type
    Secondary
    End point timeframe
    From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 152.4 weeks.
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed on Module A.
    End point values
    		 Module A, Cohort 1: GEC patients Module A, Cohort 2: 2ary resistance patients Module A, Cohort 3: 1ary resistance patients
    Number of subjects analysed
    2
    33
    42
    Units: Estimated DCR
        median (confidence interval 97.5%)
    10.83 (1.7 to 28.79)
    42.83 (28.86 to 57.14)
    44.18 (31.57 to 57.68)
    No statistical analyses for this end point

    Secondary: [Module A] Progression-free survival (PFS)

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    End point title
    		 [Module A] Progression-free survival (PFS) [18]
    End point description
    Progression-free survival (PFS) was defined as the time from first treatment administration until progressive disease (PD), according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1), or death from any cause, whichever occurred earlier. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. PFS parameters were calculated based on Kaplan-Meier estimation. Progression free survival was collected, according to the clinical trial protocol until July 2021. Treated set of the module A: all patients treated with at least one dose of trial medications.
    End point type
    Secondary
    End point timeframe
    From first drug administration until PD, death, or cut-off date of July 2021, whichever occurred earlier. Up to approximately 104.7 weeks.
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed on Module A.
    End point values
    		 Module A, Cohort 1: GEC patients Module A, Cohort 2: 2ary resistance patients Module A, Cohort 3: 1ary resistance patients
    Number of subjects analysed
    2 [19]
    33
    42
    Units: Weeks
        median (confidence interval 95%)
    5.9 (5.7 to 99999)
    6.7 (5.9 to 11.9)
    8.9 (5.7 to 16.9)
    Notes
    [19] - 99999 = not calculable due low number of events
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse event reporting and all-cause mortality: From first until last drug administration plus residual effect period (30 days). Up to approximately 192.6 weeks for module C and approximately 156.7 weeks for module A.
    Adverse event reporting additional description
    Treated set: all patients treated with at least one dose of trial medications.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.1
    Reporting groups
    Reporting group title
    Module A, Cohort 1: GEC patients
    Reporting group description
    		 Patients with locally advanced, unresectable or metastatic gastric adenocarcinoma or gastro-oesophageal adenocarcinoma, who received prior anti-PD-1 or anti-PD-L1-based treatment, were adminstered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles.

    Reporting group title
    Module C, Cohort 1: GEC patients
    Reporting group description
    		 Patients with locally advanced, unresectable or metastatic gastric adenocarcinoma or gastro-oesophageal adenocarcinoma (GEC) with at least one prior systemic treatment, who failed standard therapy, for whom no further effective options existed, and with no prior PD-1 or PD-L1-based treatment, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, in the form of i.v. infusion, on Day 1 of 21-day cycles.

    Reporting group title
    Module A, Cohort 2: 2ary resistance patients
    Reporting group description
    		 Patients with any advanced or metastatic solid tumors who had been previously treated with anti-PD-1 or anti-PD-L1-based therapies, and who progressed after achieving benefit (at least stable disease with a minimum duration of benefit of 6 months) and minimum treatment duration of 2 months without experiencing disease progression, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles.

    Reporting group title
    Module C, Cohort 2: 2ary resistance patients
    Reporting group description
    		 Patients with any advanced or metastatic solid tumor (excluding non-squamous lung cancer, non-small-cell lung cancer, and melanoma) who had received prior anti-PD-1- or anti-PD-L1-based treatment and progressed after achieving benefit (at least stable disease with a minimum duration of benefit of 4 months) and minimum treatment duration of 2 months on the previous anti-PD-1- or anti-PD-L1-based treatment without progressive disease, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along 720 mg of BI 836880 on Day 1, intravenously, on Day1 of 21-day cycles.

    Reporting group title
    Module A, Cohort 3: 1ary resistance patients
    Reporting group description
    		 Patients with select advanced or metastatic solid tumor types, who have been previously treated with previous anti-PD-1 or anti-PD-L1-based therapies without achieving benefit (stable disease for less than 6 months or progressive disease in less than 6 months), were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles.

    Reporting group title
    Module C, Cohort 3: 1ary resistance patients
    Reporting group description
    		 Patients with select advanced or metastatic solid tumors with prior anti-PD-1- or anti-PD-L1-based treatment without achieving benefit ( stable disease duration of less than 4 months or progressive disease in less than 4 months while on treatment), were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles.

    Reporting group title
    Module C, Cohort 4: CRC patients
    Reporting group description
    		 Patients with locally advanced, unresectable or metastatic second-line or greater, microsatellite-stable colorectal cancer (CRC) without prior anti-PD-1- or anti-PD-L1-based treatment, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles.

    Reporting group title
    Module C, Cohort 5: EC patients
    Reporting group description
    		 Patients with advanced endometrial carcinoma (EC), excluding microsatellite instability-high or mismatch repair deficient types, who progressed following one line of chemotherapy, were not eligible for curative surgery or radiation, and had not been previously treated with anti-PD-1- or anti-PD-L1-based therapies, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles.

    Serious adverse events
    		 Module A, Cohort 1: GEC patients Module C, Cohort 1: GEC patients Module A, Cohort 2: 2ary resistance patients Module C, Cohort 2: 2ary resistance patients Module A, Cohort 3: 1ary resistance patients Module C, Cohort 3: 1ary resistance patients Module C, Cohort 4: CRC patients Module C, Cohort 5: EC patients
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 2 (50.00%)
    11 / 28 (39.29%)
    13 / 33 (39.39%)
    18 / 30 (60.00%)
    12 / 42 (28.57%)
    12 / 28 (42.86%)
    13 / 30 (43.33%)
    11 / 18 (61.11%)
         number of deaths (all causes)
    0
    24
    29
    20
    32
    22
    17
    4
         number of deaths resulting from adverse events
    0
    1
    0
    2
    1
    4
    1
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    BASAL CELL CARCINOMA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MYELODYSPLASTIC SYNDROME
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TUMOUR ASSOCIATED FEVER
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TUMOUR THROMBOSIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    3 / 42 (7.14%)
    2 / 28 (7.14%)
    1 / 30 (3.33%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    1 / 3
    3 / 6
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HAEMORRHAGE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    HYPERTENSION
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    2 / 30 (6.67%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    6 / 6
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    DEATH
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 3
    0 / 0
    DEVICE RELATED THROMBOSIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FATIGUE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FACE OEDEMA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MALAISE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LOCALISED OEDEMA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    IMPLANT SITE PAIN
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PYREXIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PAIN
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 28 (7.14%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 6
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    OEDEMA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SYSTEMIC INFLAMMATORY RESPONSE SYNDROME
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    PROSTATITIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    ACUTE RESPIRATORY FAILURE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ASPIRATION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    2 / 30 (6.67%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 6
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DYSPNOEA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ORGANISING PNEUMONIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PLEURAL EFFUSION
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    2 / 30 (6.67%)
    1 / 42 (2.38%)
    2 / 28 (7.14%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 0
    3 / 6
    2 / 2
    3 / 9
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMOTHORAX
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    2 / 33 (6.06%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY FAILURE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    Psychiatric disorders
    DELIRIUM
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    BLOOD CREATININE INCREASED
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    6 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TROPONIN I INCREASED
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    HIP FRACTURE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FALL
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    2 / 30 (6.67%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 6
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FEMUR FRACTURE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PROCEDURAL PNEUMOTHORAX
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HUMERUS FRACTURE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    ACUTE LEFT VENTRICULAR FAILURE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ACUTE MYOCARDIAL INFARCTION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ATRIAL FIBRILLATION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ATRIOVENTRICULAR BLOCK COMPLETE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CARDIAC ARREST
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MYOCARDITIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PERICARDIAL EFFUSION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SUPRAVENTRICULAR TACHYCARDIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    CEREBROVASCULAR ACCIDENT
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SOMNOLENCE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ENCEPHALOPATHY
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    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
    0 / 0
    0 / 0
    0 / 0
    TRANSIENT ISCHAEMIC ATTACK
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SYNCOPE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BANDAEMIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    IMMUNE THROMBOCYTOPENIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NEUTROPENIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL PAIN
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    1 / 30 (3.33%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 3
    0 / 1
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ASCITES
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    2 / 30 (6.67%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 6
    0 / 0
    0 / 0
    3 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DIARRHOEA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COLITIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    3 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    1 / 30 (3.33%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ILEUS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    IMMUNE-MEDIATED ENTEROCOLITIS
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NAUSEA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LARGE INTESTINE PERFORATION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OESOPHAGEAL OBSTRUCTION
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OESOPHAGEAL PERFORATION
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 28 (7.14%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    6 / 6
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PANCREATITIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RECTAL HAEMORRHAGE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SMALL INTESTINAL OBSTRUCTION
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    2 / 30 (6.67%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    UPPER GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VOMITING
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    3 / 3
    0 / 0
    0 / 0
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    BILE DUCT STENOSIS
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BILE DUCT STONE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    BILIARY OBSTRUCTION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    DRUG-INDUCED LIVER INJURY
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HEPATIC FAILURE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    HYPERBILIRUBINAEMIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    HYPERTRANSAMINASAEMIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LIVER INJURY
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    JAUNDICE CHOLESTATIC
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 6
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    DERMATITIS BULLOUS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HAEMATURIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    IMMUNE-MEDIATED NEPHRITIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    6 / 6
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYDRONEPHROSIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NEPHRITIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    URINARY RETENTION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    URINARY TRACT OBSTRUCTION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    ADRENAL INSUFFICIENCY
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    1 / 30 (3.33%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    3 / 3
    1 / 1
    0 / 0
    0 / 0
    6 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    BACK PAIN
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    ENCEPHALITIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTROINTESTINAL INFECTION
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INFECTED FISTULA
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MENINGITIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PHARYNGITIS BACTERIAL
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    SEPSIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    1 / 28 (3.57%)
    1 / 30 (3.33%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 3
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 3
    0 / 0
    0 / 0
    PNEUMONIA ASPIRATION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    2 / 28 (7.14%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 9
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 6
    0 / 0
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    1 / 30 (3.33%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 3
    0 / 0
    0 / 3
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 3
    SKIN INFECTION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    2 / 33 (6.06%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VASCULAR DEVICE INFECTION
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 9
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    DEHYDRATION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPERCALCAEMIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPOKALAEMIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    LACTIC ACIDOSIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPONATRAEMIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Module A, Cohort 1: GEC patients Module C, Cohort 1: GEC patients Module A, Cohort 2: 2ary resistance patients Module C, Cohort 2: 2ary resistance patients Module A, Cohort 3: 1ary resistance patients Module C, Cohort 3: 1ary resistance patients Module C, Cohort 4: CRC patients Module C, Cohort 5: EC patients
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2 / 2 (100.00%)
    27 / 28 (96.43%)
    33 / 33 (100.00%)
    27 / 30 (90.00%)
    41 / 42 (97.62%)
    26 / 28 (92.86%)
    29 / 30 (96.67%)
    18 / 18 (100.00%)
    Vascular disorders
    HYPOTENSION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    6 / 33 (18.18%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    3 / 28 (10.71%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    9
    0
    0
    9
    0
    0
    HOT FLUSH
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    2 / 18 (11.11%)
         occurrences all number
    0
    0
    0
    3
    0
    3
    0
    6
    HYPERTENSION
         subjects affected / exposed
    0 / 2 (0.00%)
    3 / 28 (10.71%)
    1 / 33 (3.03%)
    9 / 30 (30.00%)
    1 / 42 (2.38%)
    6 / 28 (21.43%)
    8 / 30 (26.67%)
    7 / 18 (38.89%)
         occurrences all number
    0
    21
    2
    39
    1
    18
    45
    33
    LYMPHOEDEMA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    2 / 18 (11.11%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    0
    6
    General disorders and administration site conditions
    CHEST PAIN
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 28 (7.14%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    6
    1
    0
    0
    0
    0
    0
    ADMINISTRATION SITE REACTION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    CHILLS
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 28 (7.14%)
    4 / 33 (12.12%)
    2 / 30 (6.67%)
    2 / 42 (4.76%)
    2 / 28 (7.14%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    6
    4
    6
    2
    6
    0
    3
    EARLY SATIETY
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    3
    0
    0
    0
    0
    0
    3
    FACE OEDEMA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    3 / 30 (10.00%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    1 / 30 (3.33%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    9
    0
    3
    3
    0
    FATIGUE
         subjects affected / exposed
    1 / 2 (50.00%)
    7 / 28 (25.00%)
    12 / 33 (36.36%)
    8 / 30 (26.67%)
    19 / 42 (45.24%)
    8 / 28 (28.57%)
    11 / 30 (36.67%)
    8 / 18 (44.44%)
         occurrences all number
    1
    36
    20
    36
    26
    24
    51
    24
    INFLUENZA LIKE ILLNESS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    2 / 30 (6.67%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    6
    0
    0
    0
    0
    NON-CARDIAC CHEST PAIN
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    2 / 30 (6.67%)
    2 / 42 (4.76%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    2
    6
    2
    3
    0
    0
    OEDEMA PERIPHERAL
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 28 (7.14%)
    3 / 33 (9.09%)
    6 / 30 (20.00%)
    4 / 42 (9.52%)
    4 / 28 (14.29%)
    12 / 30 (40.00%)
    6 / 18 (33.33%)
         occurrences all number
    0
    9
    4
    27
    4
    12
    54
    18
    PAIN
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    3 / 33 (9.09%)
    0 / 30 (0.00%)
    2 / 42 (4.76%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    3
    0
    2
    0
    0
    3
    PYREXIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    4 / 33 (12.12%)
    2 / 30 (6.67%)
    5 / 42 (11.90%)
    1 / 28 (3.57%)
    1 / 30 (3.33%)
    3 / 18 (16.67%)
         occurrences all number
    0
    0
    6
    6
    6
    6
    3
    9
    SENSATION OF FOREIGN BODY
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Reproductive system and breast disorders
    BENIGN PROSTATIC HYPERPLASIA
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    DYSPNOEA EXERTIONAL
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    2 / 33 (6.06%)
    0 / 30 (0.00%)
    2 / 42 (4.76%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    3
    4
    0
    2
    0
    0
    3
    COUGH
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 28 (3.57%)
    4 / 33 (12.12%)
    3 / 30 (10.00%)
    10 / 42 (23.81%)
    0 / 28 (0.00%)
    6 / 30 (20.00%)
    5 / 18 (27.78%)
         occurrences all number
    1
    3
    4
    12
    11
    0
    33
    15
    DYSPNOEA
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 28 (7.14%)
    6 / 33 (18.18%)
    2 / 30 (6.67%)
    4 / 42 (9.52%)
    5 / 28 (17.86%)
    2 / 30 (6.67%)
    0 / 18 (0.00%)
         occurrences all number
    0
    6
    6
    9
    4
    15
    6
    0
    DYSPHONIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    1 / 30 (3.33%)
    1 / 42 (2.38%)
    1 / 28 (3.57%)
    3 / 30 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    3
    1
    3
    15
    0
    NASAL CONGESTION
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    3 / 18 (16.67%)
         occurrences all number
    0
    3
    0
    0
    1
    0
    0
    12
    LARYNGEAL PAIN
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    LOWER RESPIRATORY TRACT CONGESTION
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    2 / 42 (4.76%)
    3 / 28 (10.71%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    3
    2
    15
    0
    6
    HAEMOTHORAX
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    PLEURAL EFFUSION
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 28 (3.57%)
    1 / 33 (3.03%)
    3 / 30 (10.00%)
    2 / 42 (4.76%)
    1 / 28 (3.57%)
    2 / 30 (6.67%)
    0 / 18 (0.00%)
         occurrences all number
    1
    3
    1
    15
    2
    3
    9
    0
    RHINITIS ALLERGIC
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    2 / 18 (11.11%)
         occurrences all number
    0
    0
    0
    3
    0
    0
    3
    6
    RHINORRHOEA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    3
    0
    0
    3
    12
    SINUS CONGESTION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    Psychiatric disorders
    INSOMNIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    3 / 33 (9.09%)
    1 / 30 (3.33%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    3
    3
    1
    0
    3
    3
    ANXIETY
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    1 / 33 (3.03%)
    1 / 30 (3.33%)
    1 / 42 (2.38%)
    2 / 28 (7.14%)
    0 / 30 (0.00%)
    2 / 18 (11.11%)
         occurrences all number
    0
    3
    1
    3
    1
    6
    0
    6
    CONFUSIONAL STATE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    3 / 42 (7.14%)
    1 / 28 (3.57%)
    2 / 30 (6.67%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    3
    3
    12
    0
    DEPRESSION
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    2 / 33 (6.06%)
    2 / 30 (6.67%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    3
    2
    9
    1
    0
    0
    0
    Product issues
    DEVICE DISLOCATION
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Investigations
    BLOOD CREATININE INCREASED
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    2 / 33 (6.06%)
    4 / 30 (13.33%)
    2 / 42 (4.76%)
    3 / 28 (10.71%)
    6 / 30 (20.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    3
    3
    15
    3
    12
    24
    3
    BLOOD BILIRUBIN INCREASED
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    2 / 30 (6.67%)
    0 / 18 (0.00%)
         occurrences all number
    0
    3
    0
    0
    7
    0
    6
    0
    BLOOD ALKALINE PHOSPHATASE INCREASED
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    5 / 30 (16.67%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    24
    0
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    2 / 28 (7.14%)
    4 / 30 (13.33%)
    1 / 18 (5.56%)
         occurrences all number
    0
    3
    1
    0
    2
    6
    15
    6
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    2 / 33 (6.06%)
    1 / 30 (3.33%)
    1 / 42 (2.38%)
    2 / 28 (7.14%)
    2 / 30 (6.67%)
    3 / 18 (16.67%)
         occurrences all number
    0
    3
    3
    9
    1
    9
    9
    12
    RED BLOOD CELL COUNT INCREASED
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    PLATELET COUNT DECREASED
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    4 / 30 (13.33%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    6
    0
    0
    39
    3
    BLOOD UREA INCREASED
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    2 / 30 (6.67%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    6
    0
    VITAMIN D DECREASED
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    2 / 30 (6.67%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    6
    0
    WEIGHT DECREASED
         subjects affected / exposed
    0 / 2 (0.00%)
    5 / 28 (17.86%)
    7 / 33 (21.21%)
    2 / 30 (6.67%)
    7 / 42 (16.67%)
    4 / 28 (14.29%)
    13 / 30 (43.33%)
    3 / 18 (16.67%)
         occurrences all number
    0
    15
    11
    6
    7
    15
    45
    12
    WEIGHT INCREASED
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    1 / 42 (2.38%)
    1 / 28 (3.57%)
    1 / 30 (3.33%)
    2 / 18 (11.11%)
         occurrences all number
    0
    0
    0
    6
    1
    6
    3
    9
    Injury, poisoning and procedural complications
    CORNEAL ABRASION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    ROAD TRAFFIC ACCIDENT
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    MUSCLE STRAIN
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    3
    INFUSION RELATED REACTION
         subjects affected / exposed
    0 / 2 (0.00%)
    4 / 28 (14.29%)
    3 / 33 (9.09%)
    1 / 30 (3.33%)
    1 / 42 (2.38%)
    1 / 28 (3.57%)
    3 / 30 (10.00%)
    2 / 18 (11.11%)
         occurrences all number
    0
    12
    5
    3
    1
    6
    9
    12
    SPINAL COMPRESSION FRACTURE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    2 / 33 (6.06%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    0
    FALL
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    3 / 30 (10.00%)
    3 / 42 (7.14%)
    1 / 28 (3.57%)
    3 / 30 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    9
    3
    3
    9
    0
    WOUND
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    Cardiac disorders
    ATRIAL FIBRILLATION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    TACHYCARDIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    2 / 33 (6.06%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    0
    ATRIAL TACHYCARDIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    6
    Nervous system disorders
    APHASIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    DYSGEUSIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    1 / 42 (2.38%)
    1 / 28 (3.57%)
    3 / 30 (10.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    3
    1
    3
    12
    3
    DIZZINESS
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    6 / 33 (18.18%)
    2 / 30 (6.67%)
    4 / 42 (9.52%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    3 / 18 (16.67%)
         occurrences all number
    0
    3
    6
    6
    4
    0
    3
    12
    HEADACHE
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 28 (7.14%)
    6 / 33 (18.18%)
    4 / 30 (13.33%)
    3 / 42 (7.14%)
    2 / 28 (7.14%)
    2 / 30 (6.67%)
    4 / 18 (22.22%)
         occurrences all number
    0
    9
    7
    12
    3
    6
    6
    12
    MEMORY IMPAIRMENT
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    3
    NEUROPATHY PERIPHERAL
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    PARALYSIS RECURRENT LARYNGEAL NERVE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    PERIPHERAL SENSORY NEUROPATHY
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    3
    SYNCOPE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    3
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    0 / 2 (0.00%)
    4 / 28 (14.29%)
    5 / 33 (15.15%)
    2 / 30 (6.67%)
    6 / 42 (14.29%)
    1 / 28 (3.57%)
    1 / 30 (3.33%)
    1 / 18 (5.56%)
         occurrences all number
    0
    15
    7
    6
    13
    3
    6
    3
    THROMBOCYTOPENIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    3
    Ear and labyrinth disorders
    EAR DISCOMFORT
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    EAR PAIN
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    2 / 28 (7.14%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    6
    0
    0
    HYPOACUSIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    Eye disorders
    PERIORBITAL OEDEMA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    2 / 30 (6.67%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    2 / 18 (11.11%)
         occurrences all number
    0
    0
    0
    6
    0
    3
    0
    9
    CONJUNCTIVOCHALASIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    VISION BLURRED
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    3 / 33 (9.09%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    3
    0
    1
    0
    0
    3
    Gastrointestinal disorders
    ABDOMINAL PAIN
         subjects affected / exposed
    0 / 2 (0.00%)
    8 / 28 (28.57%)
    3 / 33 (9.09%)
    2 / 30 (6.67%)
    4 / 42 (9.52%)
    2 / 28 (7.14%)
    4 / 30 (13.33%)
    3 / 18 (16.67%)
         occurrences all number
    0
    27
    4
    9
    4
    6
    15
    9
    ABDOMINAL DISTENSION
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    2 / 33 (6.06%)
    3 / 30 (10.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    3 / 30 (10.00%)
    2 / 18 (11.11%)
         occurrences all number
    0
    3
    2
    9
    0
    0
    9
    6
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 28 (7.14%)
    1 / 33 (3.03%)
    1 / 30 (3.33%)
    1 / 42 (2.38%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    6
    1
    3
    1
    3
    0
    0
    CONSTIPATION
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 28 (7.14%)
    6 / 33 (18.18%)
    3 / 30 (10.00%)
    10 / 42 (23.81%)
    2 / 28 (7.14%)
    3 / 30 (10.00%)
    4 / 18 (22.22%)
         occurrences all number
    0
    9
    6
    9
    11
    6
    9
    12
    COLITIS
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 28 (7.14%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    3 / 18 (16.67%)
         occurrences all number
    0
    6
    0
    3
    0
    0
    0
    9
    ASCITES
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 28 (7.14%)
    1 / 33 (3.03%)
    2 / 30 (6.67%)
    1 / 42 (2.38%)
    1 / 28 (3.57%)
    2 / 30 (6.67%)
    0 / 18 (0.00%)
         occurrences all number
    0
    9
    1
    12
    1
    6
    12
    0
    EPIGASTRIC DISCOMFORT
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    FLATULENCE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    2 / 33 (6.06%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    3
    0
    DYSPHAGIA
         subjects affected / exposed
    0 / 2 (0.00%)
    3 / 28 (10.71%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    3 / 42 (7.14%)
    3 / 28 (10.71%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    9
    0
    0
    3
    9
    0
    3
    DYSPEPSIA
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    1 / 33 (3.03%)
    2 / 30 (6.67%)
    2 / 42 (4.76%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    2 / 18 (11.11%)
         occurrences all number
    0
    6
    1
    9
    2
    3
    0
    9
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    2 / 33 (6.06%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    3 / 30 (10.00%)
    2 / 18 (11.11%)
         occurrences all number
    0
    0
    2
    0
    0
    3
    9
    6
    DIARRHOEA
         subjects affected / exposed
    1 / 2 (50.00%)
    9 / 28 (32.14%)
    7 / 33 (21.21%)
    6 / 30 (20.00%)
    4 / 42 (9.52%)
    5 / 28 (17.86%)
    5 / 30 (16.67%)
    8 / 18 (44.44%)
         occurrences all number
    1
    48
    11
    18
    5
    21
    27
    45
    ORAL PAIN
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    1 / 28 (3.57%)
    1 / 30 (3.33%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    0
    1
    3
    3
    3
    ORAL DISCOMFORT
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    NAUSEA
         subjects affected / exposed
    2 / 2 (100.00%)
    5 / 28 (17.86%)
    12 / 33 (36.36%)
    7 / 30 (23.33%)
    9 / 42 (21.43%)
    3 / 28 (10.71%)
    11 / 30 (36.67%)
    7 / 18 (38.89%)
         occurrences all number
    3
    21
    19
    36
    15
    9
    42
    36
    GINGIVAL PAIN
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    3
    0
    0
    0
    0
    0
    3
    GINGIVAL BLEEDING
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    PANCREATITIS ACUTE
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    VOMITING
         subjects affected / exposed
    1 / 2 (50.00%)
    4 / 28 (14.29%)
    5 / 33 (15.15%)
    6 / 30 (20.00%)
    5 / 42 (11.90%)
    2 / 28 (7.14%)
    10 / 30 (33.33%)
    7 / 18 (38.89%)
         occurrences all number
    2
    24
    10
    24
    6
    6
    36
    42
    TOOTHACHE
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    1 / 18 (5.56%)
         occurrences all number
    0
    3
    0
    0
    0
    0
    3
    3
    STOMATITIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    2 / 42 (4.76%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    2 / 18 (11.11%)
         occurrences all number
    0
    0
    1
    0
    2
    3
    0
    15
    Hepatobiliary disorders
    CHOLECYSTITIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    HYPERTRANSAMINASAEMIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    Skin and subcutaneous tissue disorders
    DRY SKIN
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    2 / 33 (6.06%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    2
    0
    1
    0
    3
    3
    HAND DERMATITIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    PRURITUS
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 28 (7.14%)
    1 / 33 (3.03%)
    1 / 30 (3.33%)
    3 / 42 (7.14%)
    2 / 28 (7.14%)
    5 / 30 (16.67%)
    2 / 18 (11.11%)
         occurrences all number
    0
    6
    1
    3
    3
    6
    15
    6
    RASH
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    2 / 30 (6.67%)
    1 / 42 (2.38%)
    2 / 28 (7.14%)
    1 / 30 (3.33%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    6
    1
    6
    6
    3
    RASH PRURITIC
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    RASH PAPULAR
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    RASH MACULO-PAPULAR
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 28 (7.14%)
    3 / 33 (9.09%)
    1 / 30 (3.33%)
    3 / 42 (7.14%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    1 / 18 (5.56%)
         occurrences all number
    0
    6
    5
    3
    3
    0
    3
    3
    RASH ERYTHEMATOUS
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    2 / 33 (6.06%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    3
    2
    0
    0
    0
    0
    0
    Renal and urinary disorders
    HAEMATURIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    2 / 33 (6.06%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    3 / 30 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    2
    0
    1
    0
    12
    0
    DYSURIA
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    3 / 30 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    3
    0
    3
    0
    0
    9
    0
    NEPHROLITHIASIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    3 / 33 (9.09%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    3
    0
    0
    POLLAKIURIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    6
    3
    PROTEINURIA
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    5 / 30 (16.67%)
    1 / 18 (5.56%)
         occurrences all number
    0
    3
    0
    3
    0
    0
    18
    3
    NOCTURIA
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    URINARY INCONTINENCE
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    2 / 18 (11.11%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    6
    Endocrine disorders
    HYPERTHYROIDISM
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 28 (7.14%)
    3 / 33 (9.09%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    2 / 18 (11.11%)
         occurrences all number
    0
    6
    3
    0
    0
    0
    3
    6
    HYPOTHYROIDISM
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    2 / 33 (6.06%)
    4 / 30 (13.33%)
    7 / 42 (16.67%)
    3 / 28 (10.71%)
    6 / 30 (20.00%)
    5 / 18 (27.78%)
         occurrences all number
    0
    3
    2
    12
    7
    9
    21
    15
    Musculoskeletal and connective tissue disorders
    FLANK PAIN
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    4 / 33 (12.12%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    2 / 18 (11.11%)
         occurrences all number
    0
    0
    6
    3
    0
    0
    3
    6
    BACK PAIN
         subjects affected / exposed
    0 / 2 (0.00%)
    5 / 28 (17.86%)
    3 / 33 (9.09%)
    1 / 30 (3.33%)
    6 / 42 (14.29%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    2 / 18 (11.11%)
         occurrences all number
    0
    15
    3
    3
    7
    3
    0
    6
    ARTHRALGIA
         subjects affected / exposed
    0 / 2 (0.00%)
    5 / 28 (17.86%)
    8 / 33 (24.24%)
    5 / 30 (16.67%)
    5 / 42 (11.90%)
    5 / 28 (17.86%)
    2 / 30 (6.67%)
    2 / 18 (11.11%)
         occurrences all number
    0
    27
    11
    18
    6
    24
    9
    6
    GROIN PAIN
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    3
    MUSCLE SPASMS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    4 / 33 (12.12%)
    2 / 30 (6.67%)
    2 / 42 (4.76%)
    0 / 28 (0.00%)
    2 / 30 (6.67%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    4
    6
    3
    0
    6
    6
    MUSCULAR WEAKNESS
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    2 / 33 (6.06%)
    1 / 30 (3.33%)
    2 / 42 (4.76%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    2 / 18 (11.11%)
         occurrences all number
    0
    3
    3
    3
    2
    0
    0
    6
    MUSCULOSKELETAL CHEST PAIN
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    1 / 33 (3.03%)
    2 / 30 (6.67%)
    1 / 42 (2.38%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    3
    1
    9
    2
    3
    0
    0
    MYALGIA
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    2 / 33 (6.06%)
    0 / 30 (0.00%)
    3 / 42 (7.14%)
    1 / 28 (3.57%)
    1 / 30 (3.33%)
    1 / 18 (5.56%)
         occurrences all number
    0
    3
    4
    0
    3
    3
    3
    3
    NECK PAIN
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    2 / 30 (6.67%)
    0 / 42 (0.00%)
    4 / 28 (14.29%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    6
    0
    12
    0
    3
    PAIN IN EXTREMITY
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    4 / 33 (12.12%)
    0 / 30 (0.00%)
    3 / 42 (7.14%)
    1 / 28 (3.57%)
    1 / 30 (3.33%)
    4 / 18 (22.22%)
         occurrences all number
    0
    0
    7
    0
    5
    3
    3
    18
    PAIN IN JAW
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    6
    0
    3
    Infections and infestations
    CYSTITIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    COVID-19
         subjects affected / exposed
    0 / 2 (0.00%)
    3 / 28 (10.71%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    2 / 30 (6.67%)
    4 / 18 (22.22%)
         occurrences all number
    0
    9
    0
    3
    0
    3
    9
    12
    CLOSTRIDIUM DIFFICILE COLITIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    INFLUENZA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    GROIN ABSCESS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    15
    GASTROINTESTINAL VIRAL INFECTION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    FUNGAL INFECTION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    3
    FOLLICULITIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    SINUSITIS
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    3 / 33 (9.09%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    3 / 28 (10.71%)
    1 / 30 (3.33%)
    1 / 18 (5.56%)
         occurrences all number
    0
    3
    4
    0
    0
    9
    3
    3
    RHINITIS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    PNEUMONIA
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    4 / 33 (12.12%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    2 / 28 (7.14%)
    1 / 30 (3.33%)
    2 / 18 (11.11%)
         occurrences all number
    0
    6
    4
    0
    1
    6
    3
    6
    ORAL HERPES
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    9
    SKIN INFECTION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    2 / 30 (6.67%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    9
    0
    3
    0
    3
    LOWER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 2 (0.00%)
    3 / 28 (10.71%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    12
    1
    0
    0
    3
    0
    0
    TOOTH ABSCESS
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    0
    3
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    1 / 30 (3.33%)
    5 / 42 (11.90%)
    1 / 28 (3.57%)
    1 / 30 (3.33%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    6
    5
    3
    3
    6
    URINARY TRACT INFECTION
         subjects affected / exposed
    0 / 2 (0.00%)
    3 / 28 (10.71%)
    6 / 33 (18.18%)
    3 / 30 (10.00%)
    5 / 42 (11.90%)
    3 / 28 (10.71%)
    4 / 30 (13.33%)
    5 / 18 (27.78%)
         occurrences all number
    0
    9
    9
    15
    5
    9
    12
    15
    Metabolism and nutrition disorders
    DEHYDRATION
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 28 (3.57%)
    7 / 33 (21.21%)
    2 / 30 (6.67%)
    5 / 42 (11.90%)
    2 / 28 (7.14%)
    2 / 30 (6.67%)
    3 / 18 (16.67%)
         occurrences all number
    1
    3
    12
    12
    9
    6
    6
    9
    DECREASED APPETITE
         subjects affected / exposed
    0 / 2 (0.00%)
    3 / 28 (10.71%)
    8 / 33 (24.24%)
    5 / 30 (16.67%)
    9 / 42 (21.43%)
    1 / 28 (3.57%)
    5 / 30 (16.67%)
    5 / 18 (27.78%)
         occurrences all number
    0
    9
    8
    15
    10
    3
    18
    15
    HYPERCALCAEMIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    1 / 30 (3.33%)
    4 / 42 (9.52%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    3
    4
    0
    0
    0
    HYPERLIPIDAEMIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    0
    0
    3
    0
    3
    HYPERKALAEMIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    2 / 30 (6.67%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    2 / 30 (6.67%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    9
    2
    0
    6
    6
    HYPOMAGNESAEMIA
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    1 / 33 (3.03%)
    3 / 30 (10.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    1 / 18 (5.56%)
         occurrences all number
    0
    3
    1
    9
    0
    0
    3
    3
    HYPOKALAEMIA
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 28 (3.57%)
    0 / 33 (0.00%)
    2 / 30 (6.67%)
    0 / 42 (0.00%)
    2 / 28 (7.14%)
    5 / 30 (16.67%)
    0 / 18 (0.00%)
         occurrences all number
    1
    3
    0
    18
    0
    6
    15
    0
    HYPOCALCAEMIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    2 / 30 (6.67%)
    3 / 18 (16.67%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    12
    12
    HYPOALBUMINAEMIA
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 28 (3.57%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    3 / 30 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    3
    1
    0
    1
    0
    9
    0
    HYPERURICAEMIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    1 / 33 (3.03%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    4 / 30 (13.33%)
    2 / 18 (11.11%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    18
    6
    VITAMIN B12 DEFICIENCY
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    0 / 33 (0.00%)
    0 / 30 (0.00%)
    1 / 42 (2.38%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    3
    HYPONATRAEMIA
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 28 (0.00%)
    3 / 33 (9.09%)
    1 / 30 (3.33%)
    0 / 42 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    3 / 18 (16.67%)
         occurrences all number
    0
    0
    3
    6
    0
    0
    0
    30

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 May 2019
    Module A protocol amendment 1: description of the risk of infusion-related reactions with the combination of ezabenlimab and BI 754111 based on the most recent safety information; amendment of inclusion criteria to clarify that prior use of PD-1 investigational agents was not exclusionary; addition of Pre-treatment medication to the study prior to administration of the study treatment in order to reduce the risk of infusion related reactions; removal of the 5 year limit on holding trial samples to allow for more flexibility; clarification for collection of the Cycle 3 day1 tumor tissue biopsy; clarification that AEs would be reported through the entire residual effect period; addition of an interim futility analysis; update of bayesian hierarchical modelling parameters based on updated projected ORR; addition of an additional blood collection on Cycle 3 Day 1 to better track ADA levels.
    07 May 2019
    Master protocol amendment 1: addition of inclusion criteria in the synopsis; clarification of the main inclusion and exclusion criteria in the synopsis; addition of text to provide details on how to crossover to another module after progression on their previous treatment module; removal of the word multiple to clarify that there would be a limited number of modules; addition of safety and efficacy information to update the benefit-risk section of the protocol; clarification of the standard of care for advanced cancer patients; addition of text to provide safety guidance when a patient moves from one module to another; addition of text to provide guidance for male patients with partners of childbearing potential; clarification of exclusion criterion 2; modification of exclusion criteria to address UK regulatory concern; clarification of exclusion criteria 10; addition of further detail about transition timelines and patient assignment between modules after progression on a previous treatment module; update to correct the number of highly effective methods of birth control that should be used by a patient; update of language about drug-induced liver injury per Boehringer Ingelheim revised template text to clarify that all liver elevations meeting potential Hy’s Law criteria require expedited reporting as an adverse event of special interest (AESI) on the serious adverse event (SAE) form; addition of pre-treatment medication to the study prior to administration of the study treatment to reduce the risk of infusion related reactions;
    07 May 2019
    Master protocol amendment 1 (continuation): addition of what to do in the event of a Grade 3 or higher infusion related reaction; addition of a decision tree to illustrate when the Potential DILI Checklist is initiated and when it can be considered complete; addition of a guidance for the pregnant partner of a male trial participant; clarification that pharmacodynamic (PD) reporting exemptions do not apply to hepatic injury reporting; clarification that liver injury was to be reported as an AESI; collection of additional baseline date such as Baseline PD-L1 expression level, microsatellite instability (MSI), and tumor mutation burden (TMB); Update of planned analyses section on how each module would contribute to the overall development plan of each combination; addition of details on what to do in the event of an infusion related reaction.
    14 Jul 2021
    Module A protocol amendment 2: appointment of a new Coordinating Investigator to the study; clarification that ECGs were not required until the end of trial (EOT) visit unless the Investigator deemed them necessary; addition that the sponsor determined that sufficient PFS and OS data had been collected; and amendment of the follow-up visits since very few patients remained on study drug; amendment that biomarker samples would no longer be collected and analyzed.
    14 Jul 2021
    Module C protocol amendment 1: Change in Coordinating Investigator; addition of a statement to the flow chart footnotes to indicate that the date of an assessment was to be considered Day 1 of the window; modification of inclusion criterion 2 to remove the requirement for ≥1 line of prior systemic anticancer treatment in the metastatic setting; modification of inclusion criterion 3 to clarify target lesions; modification of inclusion criterion 4 to no longer allow patients with no archival tumour tissue sample and who were not biopsiable to participate in the study after discussion with the Medical Monitor; modification of exclusion criterion 2 to clarify exclusion guidelines for toxicity related to prior treatment; modification of exclusion criterion 4 and the flow chart to provide additional guidelines around blood pressure and pulse measurements; modification of exclusion criterion 6 to remove the restriction of vitamin K antagonists and other anticoagulants and to allow low-molecular-weight heparin and aspirin at doses for prevention/prophylaxis; modification of the trial design to indicate that Module values take precedence over the Master CTP.; clarification of Cohort to exclude all melanoma; clarification that, for cohort 5, hormonal monotherapy does not count as a line of therapy; addition of a window for infusion time, removal of shortening of infusion time to 30 minutes; addition of a statement, for management of an infusion-related reaction, that steroids were to be limited to prednisone 10 mg daily or equivalent;
    14 Jul 2021
    Module C protocol amendment 1 (continuation): addition of a statement to indicate that pre-treatment medications should be administered at sufficient time before initiation of infusion to allow the agents to exert their effects; addition of a drug re-administration criterion for Cycle 1; addition of a guidance for re-dosing to indicate that if the reduced dose was tolerable and deemed in the best interest of the patient, the Investigator should re-escalate; allowance of treatment with one of the 2 investigational agents if an adverse event (AE) could be clearly attributed to one of the 2 drugs; prohibition of concomitant medications known to prolong the QT interval; addition of pre-treatment to reduce the risk of infusion-related reactions; addition of the updated guidance for the EOT visit; clarification of the timing of pharmacokinetic (PK) collections from the start of ezabenlimab infusion; clarification that, before Cycle 1, blood pressure guidelines follow inclusion/exclusion criterion.
    14 Jul 2021
    Master protocol amendment 2: Change in Coordinating Investigator; modification of inclusion criterion 5 to clarify that patients with an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 could enrol; modification of inclusion criterion 6 to no longer allow patients without archival tumour tissue sample and who could not be biopsied to participate in the study; modification of exclusion criterion 3 to indicate that major surgery could be assessed by the Investigator or Medical Monitor; modification of exclusion criterion 5 to indicate that patients could be enrolled onto the study following a 7-day washout period after the end of systemic treatment for active infection; modification of exclusion criterion 12 to indicate that known, untreated, asymptomatic central nervous system metastases were to be considered an exclusion criterion.
    28 Mar 2022
    Module C protocol amendment 2: Change in The Trial Clinical Monitor; addition of treatment duration limitation was added due to program discontinuation; clarification that progression-free survival (PFS) and overall survival (OS) were no longer collected; removal of biopsies, blood samples for PK, levels of BI 836880 and ezabenlimab, biomarkers, and other assessments; modification of tumor assessments to be performed according to institutional practices and SOC; decision to terminate the trial was made; decision that no interim analyses would be performed.
    12 Jun 2023
    Master protocol amendment 3: Update of the role title from Trial Clinical Monitor to Clinical Trial Leader; BI 754091 was changed to its INN ezabenlimab; Correction of the terminology of the algorithm for patient assignment for consistency with rest of the document; Update of the role title from Team Member Medicine to Clinical Program Lead.
    13 Jun 2023
    Module C protocol amendment 3: Change in the Clinical Trial Leader; update of the role title from Trial Clinical Monitor to Clinical Trial Leader; addition of details on ezabenlimab Chemistry, Manufacturing, and Controls Tables 1 and 2 were added.

    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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