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    Clinical Trial Results:
    A Phase Ib/II, Open-Label Study of M7824 in Combination With Chemotherapy in Participants With Stage IV Non-small Cell Lung Cancer

    Summary
    EudraCT number
    		 2018-004040-28
    Trial protocol
    		 BE  
    Global end of trial date
    29 Jul 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Aug 2023
    First version publication date
    06 Aug 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    MS200647_0024
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03840915
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merck Healthcare KGaA, Darmstadt, Germany
    Sponsor organisation address
    Frankfurter Strasse 250, Darmstadt, Germany, 64293
    Public contact
    Communication Center, Merck Healthcare KGaA, Darmstadt, Germany, +49 6151725200, service@merckgroup.com
    Scientific contact
    Communication Center, Merck Healthcare KGaA, Darmstadt, Germany, +49 6151725200, service@merckgroup.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
    29 Jul 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Jul 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The main purpose of the study is to evaluate the safety and tolerability of M7824 in combination with chemotherapy.
    Protection of trial subjects
    Subject protection was ensured by following high medical and ethical standards in accordance with the principles laid down in the Declaration of Helsinki, and that are consistent with Good Clinical Practice and applicable regulations.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    02 Apr 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    France: 42
    Country: Number of subjects enrolled
    United States: 18
    Country: Number of subjects enrolled
    Belgium: 10
    Worldwide total number of subjects
    70
    EEA total number of subjects
    52
    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)
    40
    From 65 to 84 years
    30
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 127 subjects were screened out of which 70 subjects received study intervention.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort A: Bintrafusp alfa + Cisplatin/Carboplatin + Pemetrexed
    Arm description
    		 Subjects received 2400 miligrams (mg) Bintrafusp alfa along with Cisplatin 75 mg/ m^2 (per meter square) over 60 minutes or Carboplatin at area under the concentration-time Curve (AUC) 5 when combined with pemetrexed at a dose of 500 mg/ m^2 over 30 to 60 minutes every 21 days for 4 cycles (each cycle is 21 days) until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cisplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous drip use
    Dosage and administration details
    Cisplatin will be administered intravenously at a dose of 75 milligrams per meter square (mg/m^2) over 60 minutes every 21 days for 4 cycles (each cycle is 21 days).

    Investigational medicinal product name
    Bintrafusp alfa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bintrafusp alfa will be administered intravenously at a dose of 2400 mg Bintrafusp alfa every 21 days in combination with chemotherapy for 4 cycles (each cycle is 21 days) followed by up to 31 cycles in maintenance with Bintrafusp alfa and pemetrexed.

    Investigational medicinal product name
    Pemetrexed
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pemetrexed will be administered intravenously at a dose of 500 mg/ m^2 over 10 minutes every 21 days.

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Carboplatin will be administered at area under the concentration-time Curve (AUC) 5 when combined with pemetrexed over 30 to 60 minutes every 21 days for 4 cycles (each cycle is 21 days).

    Arm title
    		 CohortB:Bintrafusp alfa+Carboplatin+Paclitaxel/Nab-paclitaxel
    Arm description
    		 Subjects received 2400 mg Bintrafusp alfa along with Carboplatin at area under the concentration-time Curve (AUC) 6 when combined with nab-paclitaxel at as dose of 100 mg/m^2 over 30 to 60 minutes(Nab- paclitaxel was administered on Day 1, 8, and 15), and Paclitaxel at a dose of 200 mg/m2 over 3 hours every 21 days for 4 cycles until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nab-paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Nab-paclitaxel will be administered intravenously at as dose of 100 mg/m^2 over 30 minutes in a 21 days cycle on Day 1, 8, and 15 in each cycle for 4 cycles (each cycle is 21 days).

    Investigational medicinal product name
    Bintrafusp alfa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bintrafusp alfa will be administered intravenously at a dose of 2400 mg every 21 days in combination with chemotherapy for 4 cycles (each cycle is 21 days) followed by up to 31 cycles in maintenance with Bintrafusp alfa alone.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Paclitaxel will be administered intravenously at a dose of 200 mg/m2 over 3 hours every 3 weeks for 4 cycles (each cycle is 21 days).

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Carboplatin will be administered at area under the concentration-time Curve (AUC) 6 when combined with nab-paclitaxel over 30 to 60 minutes every 21 days for 4 cycles (each cycle is 21 days).

    Arm title
    		 CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine
    Arm description
    		 Subjects received 2400 mg Bintrafusp alfa along with Cisplatin at a dose of 75 milligrams per meter square (mg/m^2) over 60 minutes or Carboplatin at area under the concentration-time Curve (AUC) 5 when combined with gemcitabine at a dose of 1250 mg/m^2 over 30 to 60 minutes every 21 days for 4 cycles until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cisplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cisplatin will be administered intravenously at a dose of 75 milligrams per meter square (mg/m^2) over 60 minutes every 21 days for 4 cycles (each cycle is 21 days).

    Investigational medicinal product name
    Bintrafusp alfa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bintrafusp alfa will be administered intravenously at a dose of 2400 mg every 21 days in combination with chemotherapy for 4 cycles (each cycle is 21 days) followed by up to 31 cycles in maintenance with Bintrafusp alfa alone.

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Carboplatin will be administered at area under the concentration-time Curve (AUC) 5 when combined with gemcitabine over 30 to 60 minutes every 21 days for 4 cycles (each cycle is 21 days).

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Gemcitabine will be administered intravenously at a dose of 1250 mg/m^2 over 30 minutes in a 21 days cycle on Day 1, and 8, in each cycle for 4 cycles (each cycle is 21 days).

    Arm title
    		 Cohort D: Bintrafusp alfa + Docetaxel
    Arm description
    		 Subjects received 2400 mg Bintrafusp alfa along with Docetaxel at a dose of 75 mg/m^2 over 60 minutes every 21 days for 4 cycles until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Docetaxel will be administered intravenously at a dose of 75 mg/m^2 over 60 minutes every 21 days for 4 cycles (each cycle is 21 days).

    Investigational medicinal product name
    Bintrafusp alfa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bintrafusp alfa will be administered intravenously at a dose of 2400 mg every 21 days in combination with chemotherapy for 4 cycles (each cycle is 21 days) followed by up to 31 cycles in maintenance with Bintrafusp alfa alone.

    Number of subjects in period 1
    		Cohort A: Bintrafusp alfa + Cisplatin/Carboplatin + Pemetrexed CohortB:Bintrafusp alfa+Carboplatin+Paclitaxel/Nab-paclitaxel CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine Cohort D: Bintrafusp alfa + Docetaxel
    Started
    40
    9
    9
    12
    Safety Analysis Set
    40
    9
    9
    12
    Full Analysis Set
    40
    9
    9
    12
    Completed
    40
    9
    9
    12

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort A: Bintrafusp alfa + Cisplatin/Carboplatin + Pemetrexed
    Reporting group description
    		 Subjects received 2400 miligrams (mg) Bintrafusp alfa along with Cisplatin 75 mg/ m^2 (per meter square) over 60 minutes or Carboplatin at area under the concentration-time Curve (AUC) 5 when combined with pemetrexed at a dose of 500 mg/ m^2 over 30 to 60 minutes every 21 days for 4 cycles (each cycle is 21 days) until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

    Reporting group title
    CohortB:Bintrafusp alfa+Carboplatin+Paclitaxel/Nab-paclitaxel
    Reporting group description
    		 Subjects received 2400 mg Bintrafusp alfa along with Carboplatin at area under the concentration-time Curve (AUC) 6 when combined with nab-paclitaxel at as dose of 100 mg/m^2 over 30 to 60 minutes(Nab- paclitaxel was administered on Day 1, 8, and 15), and Paclitaxel at a dose of 200 mg/m2 over 3 hours every 21 days for 4 cycles until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

    Reporting group title
    CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine
    Reporting group description
    		 Subjects received 2400 mg Bintrafusp alfa along with Cisplatin at a dose of 75 milligrams per meter square (mg/m^2) over 60 minutes or Carboplatin at area under the concentration-time Curve (AUC) 5 when combined with gemcitabine at a dose of 1250 mg/m^2 over 30 to 60 minutes every 21 days for 4 cycles until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

    Reporting group title
    Cohort D: Bintrafusp alfa + Docetaxel
    Reporting group description
    		 Subjects received 2400 mg Bintrafusp alfa along with Docetaxel at a dose of 75 mg/m^2 over 60 minutes every 21 days for 4 cycles until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

    Reporting group values
    		 Cohort A: Bintrafusp alfa + Cisplatin/Carboplatin + Pemetrexed CohortB:Bintrafusp alfa+Carboplatin+Paclitaxel/Nab-paclitaxel CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine Cohort D: Bintrafusp alfa + Docetaxel Total
    Number of subjects
    		 40 9 9 12 70
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 20 6 5 9 40
        From 65-84 years
    		 20 3 4 3 30
        85 years and over
    		 0 0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 63 ( 10.3 ) 64 ( 8.7 ) 61 ( 11.2 ) 60 ( 7.7 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 9 3 4 7 23
        Male
    		 31 6 5 5 47
    Race
    Units: Subjects
        White
    		 14 6 2 3 25
        Black or African American
    		 1 2 0 0 3
        Asian
    		 0 0 0 0 0
        American Indian or Alaska Native
    		 0 0 0 0 0
        Native Hawaiian or Other Pacific
    		 0 0 0 0 0
        Not collected at this site
    		 25 1 6 9 41
        More than one race
    		 0 0 0 0 0
        Other
    		 0 0 1 0 1
        Missing
    		 0 0 0 0 0
    Ethnicity - Hispanic or Latino
    Units: Subjects
        Yes
    		 0 0 0 0 0
        No
    		 15 8 3 3 29
        Missing
    		 25 1 6 9 41

    End points

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    End points reporting groups
    Reporting group title
    Cohort A: Bintrafusp alfa + Cisplatin/Carboplatin + Pemetrexed
    Reporting group description
    		 Subjects received 2400 miligrams (mg) Bintrafusp alfa along with Cisplatin 75 mg/ m^2 (per meter square) over 60 minutes or Carboplatin at area under the concentration-time Curve (AUC) 5 when combined with pemetrexed at a dose of 500 mg/ m^2 over 30 to 60 minutes every 21 days for 4 cycles (each cycle is 21 days) until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

    Reporting group title
    CohortB:Bintrafusp alfa+Carboplatin+Paclitaxel/Nab-paclitaxel
    Reporting group description
    		 Subjects received 2400 mg Bintrafusp alfa along with Carboplatin at area under the concentration-time Curve (AUC) 6 when combined with nab-paclitaxel at as dose of 100 mg/m^2 over 30 to 60 minutes(Nab- paclitaxel was administered on Day 1, 8, and 15), and Paclitaxel at a dose of 200 mg/m2 over 3 hours every 21 days for 4 cycles until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

    Reporting group title
    CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine
    Reporting group description
    		 Subjects received 2400 mg Bintrafusp alfa along with Cisplatin at a dose of 75 milligrams per meter square (mg/m^2) over 60 minutes or Carboplatin at area under the concentration-time Curve (AUC) 5 when combined with gemcitabine at a dose of 1250 mg/m^2 over 30 to 60 minutes every 21 days for 4 cycles until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

    Reporting group title
    Cohort D: Bintrafusp alfa + Docetaxel
    Reporting group description
    		 Subjects received 2400 mg Bintrafusp alfa along with Docetaxel at a dose of 75 mg/m^2 over 60 minutes every 21 days for 4 cycles until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

    Primary: Number of Subjects With Dose-Limiting Toxicities (DLTs)

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    End point title
    		 Number of Subjects With Dose-Limiting Toxicities (DLTs) [1]
    End point description
    DLT was any AEs with Grade 4 nonhematologic toxicity or hematologic toxicity lasting >= 7 days Grade 3 nausea, vomiting, and diarrhea lasting >= 3 days Any Grade 3 or Grade 4 nonhematologic lab value leading to hospitalization or persisting for >= 7 days Grade 3 or Grade 4: grade 3 is defined as ANC < 1,000/mm3 with a temperature of > 38.3 °C grade 4 is defined as ANC< 1,000/mm3 with a temp of > 38.3°C, with life-threatening consequences Thrombocytopenia<25,000/mm3 associated with bleeding not resulting in hemodynamic instability or a life-threatening bleeding resulting in urgent intervention; Bleeding events >= Grade 3 occurring within 5 days of treatment; Prolonged delay in initiating Cycle 2 due to treatment-related toxicity; Grade 5 toxicity. DLT Set included all who received at least 90 % of the infusion and all other planned study administrations during the DLT observation period of 3 weeks and who did not discontinue the study for other reasons than DLT during the first cycle.
    End point type
    Primary
    End point timeframe
    Day 1 Week 1 up to Week 3
    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 statistical and comparison analysis were performed in single arm for this endpoint.
    End point values
    		 Cohort A: Bintrafusp alfa + Cisplatin/Carboplatin + Pemetrexed CohortB:Bintrafusp alfa+Carboplatin+Paclitaxel/Nab-paclitaxel CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine Cohort D: Bintrafusp alfa + Docetaxel
    Number of subjects analysed
    8
    8
    8
    11
    Units: Subjects
    1
    1
    0
    3
    No statistical analyses for this end point

    Primary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs ‌

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    End point title
    		 Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs ‌ [2]
    End point description
    An AE was defined as any untoward medical occurrence in a subject administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether considered related to the medicinal product or protocol-specified procedure. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAE was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious TEAEs and non-serious TEAEs. The full analysis set (FAS) included all subjects who were administered any dose of any study intervention (bintrafusp alfa or one of the chemotherapies).
    End point type
    Primary
    End point timeframe
    Time from first treatment assessed up to approximately 26 months
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical and comparison analysis were performed in single arm for this endpoint.
    End point values
    		 Cohort A: Bintrafusp alfa + Cisplatin/Carboplatin + Pemetrexed CohortB:Bintrafusp alfa+Carboplatin+Paclitaxel/Nab-paclitaxel CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine Cohort D: Bintrafusp alfa + Docetaxel
    Number of subjects analysed
    40
    9
    9
    12
    Units: Subjects
        TEAEs
    40
    9
    9
    12
        Serious TEAEs
    31
    5
    6
    9
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator (IRC)

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    End point title
    		 Percentage of Subjects With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator (IRC)
    End point description
    Percentage of subjects with confirmed objective response that is at least one overall assessment of complete response (CR) or partial response (PR) reported here. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Confirmed CR = at least 2 determinations of CR at least 4 weeks apart and before progression. Confirmed PR = at least 2 determinations of PR at least 4 weeks apart and before progression (and not qualifying for a CR). Confirmed objective response was determined according to RECIST v1.1 and as adjudicated by Investigator. The full analysis set (FAS) included all subjects who were administered any dose of any study intervention (bintrafusp alfa or one of the chemotherapies).
    End point type
    Secondary
    End point timeframe
    Time from first treatment assessed up to approximately 26 months
    End point values
    		 Cohort A: Bintrafusp alfa + Cisplatin/Carboplatin + Pemetrexed CohortB:Bintrafusp alfa+Carboplatin+Paclitaxel/Nab-paclitaxel CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine Cohort D: Bintrafusp alfa + Docetaxel
    Number of subjects analysed
    40
    9
    9
    12
    Units: Percentage of Subjects
        number (confidence interval 95%)
    45.0 (29.3 to 61.5)
    66.7 (29.9 to 92.5)
    44.4 (13.7 to 78.8)
    16.7 (2.1 to 48.4)
    No statistical analyses for this end point

    Secondary: Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator

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    End point title
    		 Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator
    End point description
    PFS was defined as the time from first administration of study intervention until date of the first documentation of disease progression (PD) or death due to any cause, whichever occurred first. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Kaplan-Meier estimates was used to calculate PFS. The full analysis set (FAS) included all subjects who were administered any dose of any study intervention (bintrafusp alfa or one of the chemotherapies)
    End point type
    Secondary
    End point timeframe
    Time from first administration of study drug until the first documentation of PD or death, assessed approximately 26 months
    End point values
    		 Cohort A: Bintrafusp alfa + Cisplatin/Carboplatin + Pemetrexed CohortB:Bintrafusp alfa+Carboplatin+Paclitaxel/Nab-paclitaxel CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine Cohort D: Bintrafusp alfa + Docetaxel
    Number of subjects analysed
    40
    9
    9
    12
    Units: months
        median (confidence interval 95%)
    5.0 (0.0 to 14.3)
    4.1 (1.2 to 17.7)
    5.4 (1.4 to 19.6)
    2.6 (1.3 to 10.4)
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR)

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    End point title
    		 Duration of Response (DOR)
    End point description
    DOR was defined for subjects with confirmed response, as the time from first documentation of confirmed objective response (Complete Response [CR] or Partial Response [PR]) according to RECIST 1.1 to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Results were calculated based on Kaplan-Meier estimates. The full analysis set (FAS) included all subjects who were administered any dose of any study intervention (bintrafusp alfa or one of the chemotherapies). 9.99999 represents no observation.
    End point type
    Secondary
    End point timeframe
    Time from first documentation of a confirmed objective response to PD or death due to any cause (assessed up to approximately 26 months)
    End point values
    		 Cohort A: Bintrafusp alfa + Cisplatin/Carboplatin + Pemetrexed CohortB:Bintrafusp alfa+Carboplatin+Paclitaxel/Nab-paclitaxel CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine Cohort D: Bintrafusp alfa + Docetaxel
    Number of subjects analysed
    40 [3]
    9 [4]
    9 [5]
    12
    Units: months
        median (confidence interval 95%)
    9.6 (3.7 to 99999)
    99999 (2.8 to 99999)
    10.5 (2.8 to 99999)
    3.4 (3.0 to 3.8)
    Notes
    [3] - Due to small number of events, estimate from Kaplan-Meier survival curves could not be derived.
    [4] - Due to small number of events, estimate from Kaplan-Meier survival curves could not be derived.
    [5] - Due to small number of events, estimate from Kaplan-Meier survival curves could not be derived.
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    OS was defined as the time from first administration of study intervention to the date of death due to any cause. The OS was analyzed by using the Kaplan-Meier method. The full analysis set (FAS) included all subjects who were administered any dose of any study intervention (bintrafusp alfa or one of the chemotherapies). 9.99999 represents no observation.
    End point type
    Secondary
    End point timeframe
    Time from first treatment assessed up to approximately 26 months
    End point values
    		 Cohort A: Bintrafusp alfa + Cisplatin/Carboplatin + Pemetrexed CohortB:Bintrafusp alfa+Carboplatin+Paclitaxel/Nab-paclitaxel CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine Cohort D: Bintrafusp alfa + Docetaxel
    Number of subjects analysed
    40
    9 [6]
    9 [7]
    12 [8]
    Units: months
        median (confidence interval 95%)
    11.4 (6.4 to 15.1)
    11.8 (1.9 to 99999)
    99999 (5.7 to 99999)
    16.5 (3.0 to 99999)
    Notes
    [6] - Due to small number of events, estimate from Kaplan-Meier survival curves could not be derived.
    [7] - Due to small number of events, estimate from Kaplan-Meier survival curves could not be derived.
    [8] - Due to small number of events, estimate from Kaplan-Meier survival curves could not be derived.
    No statistical analyses for this end point

    Secondary: Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Bintrafusp Alfa

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    End point title
    		 Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Bintrafusp Alfa
    End point description
    Ceoi was the observed concentration at the end of the infusion period. This was taken directly from the observed Bintrafusp Alfa concentration-time data.
    End point type
    Secondary
    End point timeframe
    Predose, Day 22, Day 43, Day 64 and Day 85
    End point values
    		 Cohort A: Bintrafusp alfa + Cisplatin/Carboplatin + Pemetrexed CohortB:Bintrafusp alfa+Carboplatin+Paclitaxel/Nab-paclitaxel CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine Cohort D: Bintrafusp alfa + Docetaxel
    Number of subjects analysed
    0 [9]
    0 [10]
    0 [11]
    0 [12]
    Units: microgram per milliliter (mcg/mL)
        geometric mean (geometric coefficient of variation)
    ( )
    ( )
    ( )
    ( )
    Notes
    [9] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [10] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [11] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [12] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    No statistical analyses for this end point

    Secondary: Serum Trough Concentration Levels (Ctrough) of Bintrafusp Alfa

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    End point title
    		 Serum Trough Concentration Levels (Ctrough) of Bintrafusp Alfa
    End point description
    Ctrough was the serum concentration observed immediately before next dosing.
    End point type
    Secondary
    End point timeframe
    Predose, Day 22, Day 43, Day 64 and Day 85
    End point values
    		 Cohort A: Bintrafusp alfa + Cisplatin/Carboplatin + Pemetrexed CohortB:Bintrafusp alfa+Carboplatin+Paclitaxel/Nab-paclitaxel CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine Cohort D: Bintrafusp alfa + Docetaxel
    Number of subjects analysed
    0 [13]
    0 [14]
    0 [15]
    0 [16]
    Units: mcg/mL
        geometric mean (geometric coefficient of variation)
    ( )
    ( )
    ( )
    ( )
    Notes
    [13] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [14] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [15] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [16] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    No statistical analyses for this end point

    Secondary: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Bintrafusp Alfa

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    End point title
    		 Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Bintrafusp Alfa
    End point description
    The area under the concentration-time curve (AUC) from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down).
    End point type
    Secondary
    End point timeframe
    Predose, Day 22, Day 43, Day 64 and Day 85
    End point values
    		 Cohort A: Bintrafusp alfa + Cisplatin/Carboplatin + Pemetrexed CohortB:Bintrafusp alfa+Carboplatin+Paclitaxel/Nab-paclitaxel CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine Cohort D: Bintrafusp alfa + Docetaxel
    Number of subjects analysed
    0 [17]
    0 [18]
    0 [19]
    0 [20]
    Units: nanogram hour per milliliter (ng*h/mL)
        geometric mean (geometric coefficient of variation)
    ( )
    ( )
    ( )
    ( )
    Notes
    [17] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [18] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [19] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [20] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    No statistical analyses for this end point

    Secondary: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Bintrafusp Alfa

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    End point title
    		 Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Bintrafusp Alfa
    End point description
    The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from terminal first order (elimination) rate constant determination. AUC0-inf= AUC0-tlast +Clast pred/ terminal first order (elimination) rate constant.
    End point type
    Secondary
    End point timeframe
    Predose, Day 22, Day 43, Day 64 and Day 85
    End point values
    		 Cohort A: Bintrafusp alfa + Cisplatin/Carboplatin + Pemetrexed CohortB:Bintrafusp alfa+Carboplatin+Paclitaxel/Nab-paclitaxel CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine Cohort D: Bintrafusp alfa + Docetaxel
    Number of subjects analysed
    0 [21]
    0 [22]
    0 [23]
    0 [24]
    Units: ng*h/mL
        geometric mean (geometric coefficient of variation)
    ( )
    ( )
    ( )
    ( )
    Notes
    [21] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [22] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [23] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [24] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    No statistical analyses for this end point

    Secondary: Maximum Observed Plasma Concentration (Cmax) of Bintrafusp Alfa

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    End point title
    		 Maximum Observed Plasma Concentration (Cmax) of Bintrafusp Alfa
    End point description
    Cmax was obtained directly from the concentration versus time curve.
    End point type
    Secondary
    End point timeframe
    Predose, Day 22, Day 43, Day 64 and Day 85
    End point values
    		 Cohort A: Bintrafusp alfa + Cisplatin/Carboplatin + Pemetrexed CohortB:Bintrafusp alfa+Carboplatin+Paclitaxel/Nab-paclitaxel CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine Cohort D: Bintrafusp alfa + Docetaxel
    Number of subjects analysed
    0 [25]
    0 [26]
    0 [27]
    0 [28]
    Units: ng/mL
        geometric mean (geometric coefficient of variation)
    ( )
    ( )
    ( )
    ( )
    Notes
    [25] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [26] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [27] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [28] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    No statistical analyses for this end point

    Secondary: Terminal Elimination Half-Life (T1/2) of Bintrafusp Alfa

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    End point title
    		 Terminal Elimination Half-Life (T1/2) of Bintrafusp Alfa
    End point description
    Elimination half-life determined as 0.693/terminal first order (elimination) rate constant.
    End point type
    Secondary
    End point timeframe
    Predose, Day 22, Day 43, Day 64 and Day 85
    End point values
    		 Cohort A: Bintrafusp alfa + Cisplatin/Carboplatin + Pemetrexed CohortB:Bintrafusp alfa+Carboplatin+Paclitaxel/Nab-paclitaxel CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine Cohort D: Bintrafusp alfa + Docetaxel
    Number of subjects analysed
    0 [29]
    0 [30]
    0 [31]
    0 [32]
    Units: hour
        geometric mean (geometric coefficient of variation)
    ( )
    ( )
    ( )
    ( )
    Notes
    [29] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [30] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [31] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [32] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    No statistical analyses for this end point

    Secondary: Time to Reach Maximum Plasma Concentration (Tmax) of Bintrafusp Alfa

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    End point title
    		 Time to Reach Maximum Plasma Concentration (Tmax) of Bintrafusp Alfa
    End point description
    The time to reach the maximum observed concentration collected during a dosing interval. Tmax was obtained directly from the concentration versus time curve.
    End point type
    Secondary
    End point timeframe
    Predose, Day 22, Day 43, Day 64 and Day 85
    End point values
    		 Cohort A: Bintrafusp alfa + Cisplatin/Carboplatin + Pemetrexed CohortB:Bintrafusp alfa+Carboplatin+Paclitaxel/Nab-paclitaxel CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine Cohort D: Bintrafusp alfa + Docetaxel
    Number of subjects analysed
    0 [33]
    0 [34]
    0 [35]
    0 [36]
    Units: hour
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    Notes
    [33] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [34] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [35] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    [36] - The sponsor decided to restrict the analysis of Pharmacokinetics (PK) and no PK data was collected.
    No statistical analyses for this end point

    Secondary: Number of Subjects With Positive Antidrug Antibodies (ADA)

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    End point title
    		 Number of Subjects With Positive Antidrug Antibodies (ADA)
    End point description
    Serum samples were analyzed by a validated assay method to detect the presence of antidrug antibodies (ADA). Number of subjects with positive ADA were reported.
    End point type
    Secondary
    End point timeframe
    Time from first treatment and assessed up to Disease Progression or End of Treatment
    End point values
    		 Cohort A: Bintrafusp alfa + Cisplatin/Carboplatin + Pemetrexed CohortB:Bintrafusp alfa+Carboplatin+Paclitaxel/Nab-paclitaxel CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine Cohort D: Bintrafusp alfa + Docetaxel
    Number of subjects analysed
    38
    9
    8
    12
    Units: Subjects
    9
    3
    2
    3
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Time from first treatment assessed up to approximately 26 months
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    CohortA:Bintrafusp alfa+Cisplatin/Carboplatin+Pemetrexed
    Reporting group description
    		 Subjects received 2400 miligrams (mg) Bintrafusp alfa along with Cisplatin 75 mg/ m^2 (per meter square) over 60 minutes or Carboplatin at area under the concentration-time Curve (AUC) 5 when combined with pemetrexed at a dose of 500 mg/ m^2 over 30 to 60 minutes every 21 days for 4 cycles (each cycle is 21 days) until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

    Reporting group title
    CohortB:Bintrafusp alfa+Carboplatin+PaclitaxelorNab-paclitaxel
    Reporting group description
    		 Subjects received 2400 mg Bintrafusp alfa along with Carboplatin at area under the concentration-time Curve (AUC) 6 when combined with nab-paclitaxel at as dose of 100 mg/m^2 over 30 to 60 minutes(Nab- paclitaxel was administered on Day 1, 8, and 15), and Paclitaxel at a dose of 200 mg/m2 over 3 hours every 21 days for 4 cycles until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

    Reporting group title
    CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine
    Reporting group description
    		 Subjects received 2400 mg Bintrafusp alfa along with Cisplatin at a dose of 75 milligrams per meter square (mg/m^2) over 60 minutes or Carboplatin at area under the concentration-time Curve (AUC) 5 when combined with gemcitabine at a dose of 1250 mg/m^2 over 30 to 60 minutes every 21 days for 4 cycles until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

    Reporting group title
    Cohort D: Bintrafusp alfa + Docetaxel
    Reporting group description
    		 Subjects received 2400 mg Bintrafusp alfa along with Docetaxel at a dose of 75 mg/m^2 over 60 minutes every 21 days for 4 cycles until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

    Serious adverse events
    		 CohortA:Bintrafusp alfa+Cisplatin/Carboplatin+Pemetrexed CohortB:Bintrafusp alfa+Carboplatin+PaclitaxelorNab-paclitaxel CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine Cohort D: Bintrafusp alfa + Docetaxel
    Total subjects affected by serious adverse events
         subjects affected / exposed
    31 / 40 (77.50%)
    5 / 9 (55.56%)
    6 / 9 (66.67%)
    9 / 12 (75.00%)
         number of deaths (all causes)
    23
    4
    4
    6
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to central nervous system
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Metastases to bone
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of the oral cavity
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of the tongue
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Haematoma
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemodynamic instability
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    3 / 40 (7.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumothorax
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    3 / 12 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune-mediated lung disease
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute pulmonary oedema
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute respiratory distress syndrome
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocarditis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Generalised tonic-clonic seizure
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Myelosuppression
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    2 / 12 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile bone marrow aplasia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    2 / 40 (5.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    3 / 12 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    2 / 9 (22.22%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bicytopenia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 40 (2.50%)
    2 / 9 (22.22%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic cytolysis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Tubulointerstitial nephritis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephritis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myositis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune-mediated myositis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone lesion
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematoma infection
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemophilus sepsis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia pseudomonal
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal cord infection
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Yersinia bacteraemia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    2 / 12 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 CohortA:Bintrafusp alfa+Cisplatin/Carboplatin+Pemetrexed CohortB:Bintrafusp alfa+Carboplatin+PaclitaxelorNab-paclitaxel CohortC:Bintrafusp alfa+Cisplatin/Carboplatin+Gemcitabine Cohort D: Bintrafusp alfa + Docetaxel
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    40 / 40 (100.00%)
    9 / 9 (100.00%)
    9 / 9 (100.00%)
    12 / 12 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cancer pain
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Keratoacanthoma
         subjects affected / exposed
    2 / 40 (5.00%)
    1 / 9 (11.11%)
    4 / 9 (44.44%)
    1 / 12 (8.33%)
         occurrences all number
    2
    11
    15
    1
    Papilloma
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pyogenic granuloma
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Seborrhoeic keratosis
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Skin papilloma
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Squamous cell carcinoma
         subjects affected / exposed
    3 / 40 (7.50%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    3
    1
    0
    0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Vascular disorders
    Jugular vein thrombosis
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Artery dissection
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Deep vein thrombosis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Haematoma
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypertension
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hypotension
         subjects affected / exposed
    7 / 40 (17.50%)
    3 / 9 (33.33%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    8
    3
    0
    0
    Venous thrombosis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Phlebitis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    15 / 40 (37.50%)
    1 / 9 (11.11%)
    4 / 9 (44.44%)
    7 / 12 (58.33%)
         occurrences all number
    20
    1
    10
    10
    Axillary pain
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Catheter site haemorrhage
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Catheter site inflammation
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Catheter site oedema
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Chest pain
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    3 / 12 (25.00%)
         occurrences all number
    1
    0
    1
    3
    Chills
         subjects affected / exposed
    2 / 40 (5.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    3
    1
    0
    0
    Xerosis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    1
    1
    Pyrexia
         subjects affected / exposed
    11 / 40 (27.50%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    4 / 12 (33.33%)
         occurrences all number
    16
    1
    0
    6
    Pain
         subjects affected / exposed
    2 / 40 (5.00%)
    2 / 9 (22.22%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    2
    2
    0
    1
    Oedema peripheral
         subjects affected / exposed
    6 / 40 (15.00%)
    0 / 9 (0.00%)
    2 / 9 (22.22%)
    3 / 12 (25.00%)
         occurrences all number
    8
    0
    3
    3
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Mucosal inflammation
         subjects affected / exposed
    4 / 40 (10.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    5
    0
    0
    1
    Malaise
         subjects affected / exposed
    3 / 40 (7.50%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    3
    0
    2
    0
    Infusion site extravasation
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    Hyperthermia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    1
    1
    Hernia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    General physical health deterioration
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    0
    1
    Gait disturbance
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Fatigue
         subjects affected / exposed
    7 / 40 (17.50%)
    3 / 9 (33.33%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    9
    3
    1
    0
    Face oedema
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    2 / 9 (22.22%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Contrast media allergy
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    Reproductive system and breast disorders
    Breast cyst
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Penile erosion
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Hiccups
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Cough
         subjects affected / exposed
    6 / 40 (15.00%)
    3 / 9 (33.33%)
    1 / 9 (11.11%)
    2 / 12 (16.67%)
         occurrences all number
    6
    4
    1
    3
    Dysphonia
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 9 (11.11%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    1
    0
    Dyspnoea
         subjects affected / exposed
    6 / 40 (15.00%)
    1 / 9 (11.11%)
    1 / 9 (11.11%)
    5 / 12 (41.67%)
         occurrences all number
    6
    1
    1
    6
    Dyspnoea exertional
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Epistaxis
         subjects affected / exposed
    10 / 40 (25.00%)
    1 / 9 (11.11%)
    4 / 9 (44.44%)
    4 / 12 (33.33%)
         occurrences all number
    14
    1
    6
    5
    Haemoptysis
         subjects affected / exposed
    2 / 40 (5.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    4 / 12 (33.33%)
         occurrences all number
    2
    1
    0
    4
    Lower respiratory tract congestion
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Increased viscosity of bronchial secretion
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Nasal dryness
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    4 / 40 (10.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    4
    0
    0
    0
    Pleural effusion
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pleuritic pain
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Productive cough
         subjects affected / exposed
    3 / 40 (7.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Pulmonary embolism
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    1
    0
    Pulmonary oedema
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rales
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Respiratory distress
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Upper-airway cough syndrome
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Wheezing
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hypoxia
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Immune-mediated lung disease
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Lung disorder
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Psychiatric disorders
    Sleep disorder
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Agitation
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Anxiety
         subjects affected / exposed
    4 / 40 (10.00%)
    0 / 9 (0.00%)
    2 / 9 (22.22%)
    0 / 12 (0.00%)
         occurrences all number
    4
    0
    2
    0
    Depression
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hallucination
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Insomnia
         subjects affected / exposed
    6 / 40 (15.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    6
    1
    0
    0
    Pica
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Restlessness
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    3 / 9 (33.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    5
    0
    Amylase increased
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    3 / 9 (33.33%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    5
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    4 / 40 (10.00%)
    0 / 9 (0.00%)
    2 / 9 (22.22%)
    1 / 12 (8.33%)
         occurrences all number
    4
    0
    3
    1
    SARS-CoV-2 test positive
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    1
    0
    Blood creatinine increased
         subjects affected / exposed
    3 / 40 (7.50%)
    0 / 9 (0.00%)
    3 / 9 (33.33%)
    2 / 12 (16.67%)
         occurrences all number
    3
    0
    6
    2
    Blood fibrinogen increased
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    2 / 9 (22.22%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    3
    0
    Blood thyroid stimulating hormone decreased
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    3
    0
    Blood urea increased
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Blood uric acid increased
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Eosinophil count increased
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Platelet count decreased
         subjects affected / exposed
    3 / 40 (7.50%)
    0 / 9 (0.00%)
    2 / 9 (22.22%)
    1 / 12 (8.33%)
         occurrences all number
    6
    0
    5
    1
    Neutrophil count increased
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    1
    Neutrophil count decreased
         subjects affected / exposed
    2 / 40 (5.00%)
    3 / 9 (33.33%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    7
    5
    3
    0
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Lipase increased
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Haematocrit decreased
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gastric pH decreased
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    3 / 40 (7.50%)
    0 / 9 (0.00%)
    2 / 9 (22.22%)
    2 / 12 (16.67%)
         occurrences all number
    3
    0
    2
    2
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    4
    0
    Sputum abnormal
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Weight decreased
         subjects affected / exposed
    5 / 40 (12.50%)
    1 / 9 (11.11%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    9
    1
    1
    0
    Weight increased
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    White blood cell count decreased
         subjects affected / exposed
    3 / 40 (7.50%)
    4 / 9 (44.44%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    12
    6
    3
    0
    Injury, poisoning and procedural complications
    Ilium fracture
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Head injury
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Fall
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Eye contusion
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Contusion
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Infusion related reaction
         subjects affected / exposed
    3 / 40 (7.50%)
    1 / 9 (11.11%)
    1 / 9 (11.11%)
    1 / 12 (8.33%)
         occurrences all number
    3
    1
    1
    1
    Traumatic haematoma
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Spinal fracture
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin laceration
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Skin abrasion
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Radiation skin injury
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cardiac disorders
    Tricuspid valve incompetence
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Tachycardia
         subjects affected / exposed
    1 / 40 (2.50%)
    3 / 9 (33.33%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    3
    0
    1
    Sinus tachycardia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Mitral valve incompetence
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cardiac failure
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    0
    1
    Atrial flutter
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Atrial fibrillation
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    2
    0
    0
    1
    Angina pectoris
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Myocarditis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Dizziness
         subjects affected / exposed
    1 / 40 (2.50%)
    2 / 9 (22.22%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    3
    0
    1
    Dizziness postural
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Dysgeusia
         subjects affected / exposed
    4 / 40 (10.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    1 / 12 (8.33%)
         occurrences all number
    4
    0
    1
    1
    Headache
         subjects affected / exposed
    4 / 40 (10.00%)
    1 / 9 (11.11%)
    1 / 9 (11.11%)
    2 / 12 (16.67%)
         occurrences all number
    5
    1
    1
    3
    Hypoaesthesia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Motor dysfunction
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Neuralgia
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Paraesthesia
         subjects affected / exposed
    3 / 40 (7.50%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    3
    2
    0
    0
    Peripheral motor neuropathy
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 40 (0.00%)
    2 / 9 (22.22%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    2
    0
    1
    Presyncope
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Restless legs syndrome
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Sciatica
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    1
    1
    Taste disorder
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Tremor
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    2 / 9 (22.22%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Hyperleukocytosis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    0
    1
    Thrombocytosis
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    2 / 9 (22.22%)
    1 / 12 (8.33%)
         occurrences all number
    2
    0
    2
    1
    Thrombocytopenia
         subjects affected / exposed
    7 / 40 (17.50%)
    2 / 9 (22.22%)
    4 / 9 (44.44%)
    0 / 12 (0.00%)
         occurrences all number
    13
    3
    6
    0
    Spontaneous haematoma
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pancytopenia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Neutropenia
         subjects affected / exposed
    5 / 40 (12.50%)
    1 / 9 (11.11%)
    5 / 9 (55.56%)
    2 / 12 (16.67%)
         occurrences all number
    7
    3
    5
    2
    Myelosuppression
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Lymphopenia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    2 / 9 (22.22%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    5
    1
    Lymphadenopathy
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    1
    Anaemia
         subjects affected / exposed
    20 / 40 (50.00%)
    6 / 9 (66.67%)
    9 / 9 (100.00%)
    9 / 12 (75.00%)
         occurrences all number
    28
    12
    9
    9
    Eosinophilia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Febrile neutropenia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Ear and labyrinth disorders
    Hypoacusis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Ear discomfort
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Tinnitus
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Eye disorders
    Blepharospasm
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Blepharitis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Diplopia
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Xerophthalmia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Visual impairment
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Visual acuity reduced
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Vision blurred
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Lacrimation increased
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Dry eye
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Gastrointestinal disorders
    Cheilitis
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Aphthous ulcer
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    1
    0
    Abdominal pain lower
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Abdominal pain
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    2 / 12 (16.67%)
         occurrences all number
    2
    0
    1
    2
    Abdominal discomfort
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Colitis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    0
    1
    Mouth haemorrhage
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Diarrhoea
         subjects affected / exposed
    13 / 40 (32.50%)
    3 / 9 (33.33%)
    2 / 9 (22.22%)
    6 / 12 (50.00%)
         occurrences all number
    15
    3
    2
    10
    Dry mouth
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    4 / 12 (33.33%)
         occurrences all number
    2
    0
    1
    4
    Duodenitis
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Melaena
         subjects affected / exposed
    2 / 40 (5.00%)
    1 / 9 (11.11%)
    1 / 9 (11.11%)
    1 / 12 (8.33%)
         occurrences all number
    2
    2
    1
    1
    Haemorrhoids
         subjects affected / exposed
    3 / 40 (7.50%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    3
    1
    0
    1
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Haematochezia
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Gingival bleeding
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    2 / 9 (22.22%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    2
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 40 (0.00%)
    2 / 9 (22.22%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Gastritis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gastric ulcer
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Enteritis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dysphagia
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Dyspepsia
         subjects affected / exposed
    4 / 40 (10.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    1 / 12 (8.33%)
         occurrences all number
    5
    0
    1
    1
    Constipation
         subjects affected / exposed
    7 / 40 (17.50%)
    6 / 9 (66.67%)
    2 / 9 (22.22%)
    2 / 12 (16.67%)
         occurrences all number
    10
    10
    3
    2
    Oral mucosa erosion
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Oral pain
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rectal haemorrhage
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Stomatitis
         subjects affected / exposed
    5 / 40 (12.50%)
    2 / 9 (22.22%)
    0 / 9 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    5
    6
    0
    2
    Stomatitis haemorrhagic
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Subileus
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Tongue dry
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Toothache
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    1
    2
    Vomiting
         subjects affected / exposed
    7 / 40 (17.50%)
    1 / 9 (11.11%)
    2 / 9 (22.22%)
    5 / 12 (41.67%)
         occurrences all number
    12
    1
    4
    6
    Nausea
         subjects affected / exposed
    21 / 40 (52.50%)
    3 / 9 (33.33%)
    6 / 9 (66.67%)
    5 / 12 (41.67%)
         occurrences all number
    29
    3
    11
    5
    Oesophageal pain
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Oesophagitis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hepatobiliary disorders
    Hepatic cytolysis
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Cholestasis
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Hepatotoxicity
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hepatitis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Actinic keratosis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Alopecia
         subjects affected / exposed
    2 / 40 (5.00%)
    2 / 9 (22.22%)
    0 / 9 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    2
    2
    0
    2
    Rash
         subjects affected / exposed
    7 / 40 (17.50%)
    2 / 9 (22.22%)
    2 / 9 (22.22%)
    2 / 12 (16.67%)
         occurrences all number
    9
    2
    3
    3
    Dermal cyst
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Dermatitis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dermatitis acneiform
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Dermatitis bullous
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Drug eruption
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dry skin
         subjects affected / exposed
    5 / 40 (12.50%)
    0 / 9 (0.00%)
    2 / 9 (22.22%)
    0 / 12 (0.00%)
         occurrences all number
    5
    0
    3
    0
    Eczema
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    2 / 9 (22.22%)
    0 / 12 (0.00%)
         occurrences all number
    5
    0
    8
    0
    Erythema
         subjects affected / exposed
    4 / 40 (10.00%)
    0 / 9 (0.00%)
    2 / 9 (22.22%)
    2 / 12 (16.67%)
         occurrences all number
    6
    0
    2
    3
    Hyperkeratosis
         subjects affected / exposed
    3 / 40 (7.50%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    4
    0
    1
    0
    Intertrigo
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Keratosis pilaris
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Papule
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Pemphigoid
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Petechiae
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pruritus
         subjects affected / exposed
    15 / 40 (37.50%)
    3 / 9 (33.33%)
    6 / 9 (66.67%)
    2 / 12 (16.67%)
         occurrences all number
    22
    3
    11
    2
    Purpura
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blister
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rash erythematous
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    1
    1
    Rash papular
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    2
    Rash pruritic
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin discolouration
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Skin hyperpigmentation
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin lesion
         subjects affected / exposed
    2 / 40 (5.00%)
    1 / 9 (11.11%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    4
    6
    12
    0
    Skin lesion inflammation
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Subcutaneous emphysema
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Toxic skin eruption
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Urticaria
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Xeroderma
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    2 / 9 (22.22%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    3
    0
    Rash maculo-papular
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    0
    1
    Haematuria
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    2 / 9 (22.22%)
    1 / 12 (8.33%)
         occurrences all number
    2
    0
    2
    1
    Nephritis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Renal failure
         subjects affected / exposed
    4 / 40 (10.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    4
    0
    1
    0
    Renal impairment
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Urinary retention
         subjects affected / exposed
    2 / 40 (5.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Dysuria
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    1
    Endocrine disorders
    Immune-mediated hyperthyroidism
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hypothyroidism
         subjects affected / exposed
    4 / 40 (10.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    4
    0
    1
    0
    Hyperthyroidism
         subjects affected / exposed
    4 / 40 (10.00%)
    0 / 9 (0.00%)
    2 / 9 (22.22%)
    0 / 12 (0.00%)
         occurrences all number
    4
    0
    2
    0
    Musculoskeletal and connective tissue disorders
    Neck pain
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    2 / 9 (22.22%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Arthralgia
         subjects affected / exposed
    4 / 40 (10.00%)
    2 / 9 (22.22%)
    0 / 9 (0.00%)
    3 / 12 (25.00%)
         occurrences all number
    5
    2
    0
    3
    Back pain
         subjects affected / exposed
    2 / 40 (5.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    2
    1
    0
    2
    Bone pain
         subjects affected / exposed
    0 / 40 (0.00%)
    2 / 9 (22.22%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Immune-mediated myositis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Muscle spasms
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    0
    1
    Muscular weakness
         subjects affected / exposed
    1 / 40 (2.50%)
    2 / 9 (22.22%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    2
    2
    0
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Musculoskeletal pain
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    4 / 12 (33.33%)
         occurrences all number
    0
    1
    0
    5
    Myalgia
         subjects affected / exposed
    1 / 40 (2.50%)
    2 / 9 (22.22%)
    2 / 9 (22.22%)
    0 / 12 (0.00%)
         occurrences all number
    1
    3
    2
    0
    Myositis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Osteonecrosis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    3 / 40 (7.50%)
    1 / 9 (11.11%)
    2 / 9 (22.22%)
    0 / 12 (0.00%)
         occurrences all number
    3
    1
    2
    0
    Spinal pain
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Herpes simplex
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Fungal skin infection
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Folliculitis
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    4
    0
    0
    1
    Device related infection
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Conjunctivitis
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Cellulitis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Candida infection
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Bronchitis
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    2
    0
    0
    2
    Abscess intestinal
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Gingivitis
         subjects affected / exposed
    3 / 40 (7.50%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    3
    0
    1
    0
    Furuncle
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pneumonia
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    4 / 40 (10.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    4
    0
    0
    0
    Paronychia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Oral herpes
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Oral fungal infection
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    0
    1
    Oral candidiasis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    0
    1
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Hordeolum
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pneumonia pseudomonal
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Rash pustular
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Rhinitis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Sepsis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin infection
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Staphylococcal infection
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Tooth infection
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Periodontitis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Yersinia bacteraemia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Wound infection
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Vulvovaginal mycotic infection
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Metabolism and nutrition disorders
    Hyperkalaemia
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Hypermagnesaemia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hypernatraemia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hyperuricaemia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hypoalbuminaemia
         subjects affected / exposed
    3 / 40 (7.50%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    3 / 12 (25.00%)
         occurrences all number
    3
    0
    2
    3
    Hypocalcaemia
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    Hypochloraemia
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Cell death
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Decreased appetite
         subjects affected / exposed
    7 / 40 (17.50%)
    3 / 9 (33.33%)
    4 / 9 (44.44%)
    6 / 12 (50.00%)
         occurrences all number
    9
    4
    4
    6
    Dehydration
         subjects affected / exposed
    2 / 40 (5.00%)
    2 / 9 (22.22%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    4
    0
    0
    Diabetes mellitus
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Folate deficiency
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Hypercalcaemia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    1
    1
    Hyperglycaemia
         subjects affected / exposed
    3 / 40 (7.50%)
    1 / 9 (11.11%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    3
    2
    0
    0
    Hypokalaemia
         subjects affected / exposed
    6 / 40 (15.00%)
    3 / 9 (33.33%)
    1 / 9 (11.11%)
    2 / 12 (16.67%)
         occurrences all number
    9
    6
    2
    2
    Hyponatraemia
         subjects affected / exposed
    3 / 40 (7.50%)
    0 / 9 (0.00%)
    1 / 9 (11.11%)
    1 / 12 (8.33%)
         occurrences all number
    4
    0
    1
    1
    Hypophosphataemia
         subjects affected / exposed
    1 / 40 (2.50%)
    2 / 9 (22.22%)
    1 / 9 (11.11%)
    1 / 12 (8.33%)
         occurrences all number
    1
    2
    1
    1
    Hypoproteinaemia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Iron deficiency
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Lactic acidosis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 9 (0.00%)
    0 / 9 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hypomagnesaemia
         subjects affected / exposed
    3 / 40 (7.50%)
    2 / 9 (22.22%)
    1 / 9 (11.11%)
    0 / 12 (0.00%)
         occurrences all number
    4
    5
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Jul 2019
    Key changes to the protocol were done to clarify eligibility criteria, to modify nonserious adverse events of special interest reporting and to update safety profile of bintrafusp alfa according to Investigators brochure.
    12 Nov 2019
    The purpose of the amendment was to add additional 3 cohorts to explore the safety and efficacy of bintrafusp alfa with new anti-cancer agents.
    22 Dec 2021
    The primary purpose of this amendment was to align with the Investigator Brochure and to update the risk classification and minimization measures.

    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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