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    Clinical Trial Results:
    A Phase 1b/2 Clinical Study of Intratumoral Administration of V937 in Combination with Pembrolizumab (MK-3475) in Participants with Advanced/Metastatic Solid Tumors

    Summary
    EudraCT number
    		 2020-001908-42
    Trial protocol
    		 NO   HU   DE   PL   PT   IT  
    Global end of trial date
    25 Jul 2023

    Results information
    Results version number
    		 v2(current)
    This version publication date
    21 Sep 2024
    First version publication date
    04 Aug 2024
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    V937-013
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04521621
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 jRCT2033200191: jRCT
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme LLC
    Sponsor organisation address
    126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ, United States, 07065
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.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
    25 Jul 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    25 Jul 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    25 Jul 2023
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The purpose of this study is to evaluate the safety, tolerability, and efficacy in participants with advanced/metastatic or recurrent malignancies who receive gebasaxturev (V937) in combination with pembrolizumab (MK-3475). The primary objective for Part 1 is to evaluate the objective response rate, and the primary objective for Part 2 is to determine the safety and tolerability of gebasaxturev administered in combination with pembrolizumab. With Amendment 4, this study will be terminated once all participants who have completed or discontinued gebasaxturev treatment and are only receiving pembrolizumab may be enrolled in a pembrolizumab extension study, if available, to continue pembrolizumab monotherapy for up to 35 cycles from first pembrolizumab dose on V937-013.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    28 Oct 2020
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 6
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Spain: 16
    Country: Number of subjects enrolled
    France: 12
    Country: Number of subjects enrolled
    Hungary: 2
    Country: Number of subjects enrolled
    Israel: 9
    Country: Number of subjects enrolled
    Japan: 2
    Country: Number of subjects enrolled
    Norway: 7
    Country: Number of subjects enrolled
    Peru: 2
    Country: Number of subjects enrolled
    Poland: 1
    Country: Number of subjects enrolled
    Portugal: 4
    Country: Number of subjects enrolled
    Taiwan: 11
    Country: Number of subjects enrolled
    United States: 3
    Worldwide total number of subjects
    76
    EEA total number of subjects
    43
    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)
    43
    From 65 to 84 years
    24
    85 years and over
    9

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 76 participants were allocated and 75 participants received study intervention. Enrollment was also planned to Part 2 Cohort D (participants with hepatocellular carcinoma (HCC) solid tumors) and Part 2 Cohort E (participants with gastric carcinoma solid tumors); however, the study was terminated before enrollment into these arms began.

    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
    		 Part 1, Cohort A: Triple-Negative Breast Cancer
    Arm description
    		 Participants with triple-negative breast cancer (TNBC) solid tumors received 3 X 10^8 50% tissue culture infectious dose (TCID50) of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475 KEYTRUDA®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants receive pembrolizumab intravenously for 1 28-day cycle followed by 34 21-day cycles.

    Investigational medicinal product name
    Gebasaxturev
    Investigational medicinal product code
    Other name
    Coxsackievirus A21(CVA21) Formerly known asCAVATAK® CAV21 V937
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intratumoral use
    Dosage and administration details
    Participants receive gebasaxturev intratumorally for 1 28-day cycle followed by 7 21-day cycles.

    Arm title
    		 Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma
    Arm description
    		 Participants with head and neck squamous cell carcinoma (HNSCC) solid tumors received 3 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475 KEYTRUDA®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants receive pembrolizumab intravenously for 1 28-day cycle followed by 34 21-day cycles.

    Investigational medicinal product name
    Gebasaxturev
    Investigational medicinal product code
    Other name
    Coxsackievirus A21(CVA21) Formerly known asCAVATAK® CAV21 V937
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intratumoral use
    Dosage and administration details
    Participants receive gebasaxturev intratumorally for 1 28-day cycle followed by 7 21-day cycles.

    Arm title
    		 Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma
    Arm description
    		 Participants with cutaneous squamous cell carcinoma (cSCC) solid tumors received 3 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475 KEYTRUDA®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants receive pembrolizumab intravenously for 1 28-day cycle followed by 34 21-day cycles.

    Investigational medicinal product name
    Gebasaxturev
    Investigational medicinal product code
    Other name
    Coxsackievirus A21(CVA21) Formerly known asCAVATAK® CAV21 V937
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intratumoral use
    Dosage and administration details
    Participants receive gebasaxturev intratumorally for 1 28-day cycle followed by 7 21-day cycles.

    Arm title
    		 Part 2 Dose Level 1, Solid Tumors + Liver Metastases
    Arm description
    		 Participants with solid tumors with liver metastases received 3 X 10^7 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475 KEYTRUDA®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants receive pembrolizumab intravenously for 1 28-day cycle followed by 34 21-day cycles.

    Investigational medicinal product name
    Gebasaxturev
    Investigational medicinal product code
    Other name
    Coxsackievirus A21(CVA21) Formerly known asCAVATAK® CAV21 V937
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intratumoral use
    Dosage and administration details
    Participants receive gebasaxturev intratumorally for 1 28-day cycle followed by 7 21-day cycles.

    Arm title
    		 Part 2 Dose Level 2, Solid Tumors + Liver Metastases
    Arm description
    		 Participants with solid tumors with liver metastases received 1 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475 KEYTRUDA®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants receive pembrolizumab intravenously for 1 28-day cycle followed by 34 21-day cycles.

    Investigational medicinal product name
    Gebasaxturev
    Investigational medicinal product code
    Other name
    Coxsackievirus A21(CVA21) Formerly known asCAVATAK® CAV21 V937
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intratumoral use
    Dosage and administration details
    Participants receive gebasaxturev intratumorally for 1 28-day cycle followed by 7 21-day cycles.

    Arm title
    		 Part 2 Dose Level 3, Solid Tumors + Liver Metastases
    Arm description
    		 Participants with solid tumors with liver metastases received 3 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475 KEYTRUDA®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants receive pembrolizumab intravenously for 1 28-day cycle followed by 34 21-day cycles.

    Investigational medicinal product name
    Gebasaxturev
    Investigational medicinal product code
    Other name
    Coxsackievirus A21(CVA21) Formerly known asCAVATAK® CAV21 V937
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intratumoral use
    Dosage and administration details
    Participants receive gebasaxturev intratumorally for 1 28-day cycle followed by 7 21-day cycles.

    Number of subjects in period 1
    		Part 1, Cohort A: Triple-Negative Breast Cancer Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma Part 2 Dose Level 1, Solid Tumors + Liver Metastases Part 2 Dose Level 2, Solid Tumors + Liver Metastases Part 2 Dose Level 3, Solid Tumors + Liver Metastases
    Started
    22
    14
    17
    6
    3
    14
    Treated
    21
    14
    17
    6
    3
    14
    Completed
    0
    0
    0
    0
    0
    0
    Not completed
    22
    14
    17
    6
    3
    14
         Consent withdrawn by subject
    -
    -
    1
    1
    -
    -
         Death
    17
    8
    8
    5
    2
    7
         Allocated in error without study intervention
    1
    -
    -
    -
    -
    -
         Study Terminated by Sponsor
    4
    6
    8
    -
    1
    7

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Part 1, Cohort A: Triple-Negative Breast Cancer
    Reporting group description
    		 Participants with triple-negative breast cancer (TNBC) solid tumors received 3 X 10^8 50% tissue culture infectious dose (TCID50) of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.

    Reporting group title
    Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma
    Reporting group description
    		 Participants with head and neck squamous cell carcinoma (HNSCC) solid tumors received 3 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.

    Reporting group title
    Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma
    Reporting group description
    		 Participants with cutaneous squamous cell carcinoma (cSCC) solid tumors received 3 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.

    Reporting group title
    Part 2 Dose Level 1, Solid Tumors + Liver Metastases
    Reporting group description
    		 Participants with solid tumors with liver metastases received 3 X 10^7 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.

    Reporting group title
    Part 2 Dose Level 2, Solid Tumors + Liver Metastases
    Reporting group description
    		 Participants with solid tumors with liver metastases received 1 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.

    Reporting group title
    Part 2 Dose Level 3, Solid Tumors + Liver Metastases
    Reporting group description
    		 Participants with solid tumors with liver metastases received 3 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.

    Reporting group values
    		 Part 1, Cohort A: Triple-Negative Breast Cancer Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma Part 2 Dose Level 1, Solid Tumors + Liver Metastases Part 2 Dose Level 2, Solid Tumors + Liver Metastases Part 2 Dose Level 3, Solid Tumors + Liver Metastases Total
    Number of subjects
    		 22 14 17 6 3 14 76
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0 0
        Adults (18-64 years)
    		 17 9 3 5 2 7 43
        From 65-84 years
    		 5 5 5 1 1 7 24
        85 years and over
    		 0 0 9 0 0 0 9
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 55.5 ( 11.5 ) 59.7 ( 13.1 ) 80.6 ( 12.8 ) 54.7 ( 12.5 ) 58.3 ( 8.3 ) 57.8 ( 14.1 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 22 2 6 3 2 10 45
        Male
    		 0 12 11 3 1 4 31
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0 0 0
        Asian
    		 0 7 0 1 2 4 14
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0 0 0
        Black or African American
    		 0 0 0 0 0 0 0
        White
    		 20 7 14 5 1 8 55
        More than one race
    		 2 0 0 0 0 0 2
        Unknown or Not Reported
    		 0 0 3 0 0 2 5
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 4 0 0 0 0 0 4
        Not Hispanic or Latino
    		 18 14 13 6 3 11 65
        Unknown or Not Reported
    		 0 0 4 0 0 3 7

    End points

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    End points reporting groups
    Reporting group title
    Part 1, Cohort A: Triple-Negative Breast Cancer
    Reporting group description
    		 Participants with triple-negative breast cancer (TNBC) solid tumors received 3 X 10^8 50% tissue culture infectious dose (TCID50) of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.

    Reporting group title
    Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma
    Reporting group description
    		 Participants with head and neck squamous cell carcinoma (HNSCC) solid tumors received 3 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.

    Reporting group title
    Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma
    Reporting group description
    		 Participants with cutaneous squamous cell carcinoma (cSCC) solid tumors received 3 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.

    Reporting group title
    Part 2 Dose Level 1, Solid Tumors + Liver Metastases
    Reporting group description
    		 Participants with solid tumors with liver metastases received 3 X 10^7 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.

    Reporting group title
    Part 2 Dose Level 2, Solid Tumors + Liver Metastases
    Reporting group description
    		 Participants with solid tumors with liver metastases received 1 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.

    Reporting group title
    Part 2 Dose Level 3, Solid Tumors + Liver Metastases
    Reporting group description
    		 Participants with solid tumors with liver metastases received 3 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.

    Primary: Part 1: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator

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    End point title
    		 Part 1: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator [1]
    End point description
    ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions and no new lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by investigator. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection does not render a lesion non-evaluable. The analysis population consisted of all allocated participants in Part 1 with a baseline scan that demonstrated measurable disease and who received at least 1 dose of study intervention.
    End point type
    Primary
    End point timeframe
    Up to approximately 30 months
    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: Per protocol, no statistical analyses were planned for this endpoint.
    End point values
    		 Part 1, Cohort A: Triple-Negative Breast Cancer Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma Part 2 Dose Level 1, Solid Tumors + Liver Metastases Part 2 Dose Level 2, Solid Tumors + Liver Metastases Part 2 Dose Level 3, Solid Tumors + Liver Metastases
    Number of subjects analysed
    21
    14
    17
    0 [2]
    0 [3]
    0 [4]
    Units: Percentage of Participants
        number (confidence interval 95%)
    0.0 (0.0 to 16.1)
    35.7 (12.8 to 64.9)
    64.7 (38.3 to 85.8)
    ( to )
    ( to )
    ( to )
    Notes
    [2] - Per protocol, only participants in Part 1 were analyzed in this outcome measure.
    [3] - Per protocol, only participants in Part 1 were analyzed in this outcome measure.
    [4] - Per protocol, only participants in Part 1 were analyzed in this outcome measure.
    No statistical analyses for this end point

    Primary: Number of Participants who Experienced a Dose-Limiting Toxicity (DLT)

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    End point title
    		 Number of Participants who Experienced a Dose-Limiting Toxicity (DLT) [5]
    End point description
    The following toxicities during DLT evaluation period were considered a DLT, if assessed by investigator to be possibly, probably, or definitely related to treatment: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days, except Gr 3 thrombocytopenia (if associated with clinically significant bleeding) or any grade febrile neutropenia; nonhematologic adverse event (AE) ≥ Gr 3 (with exceptions); Gr 3 or 4 nonhematologic lab abnormality (if medical intervention is required, leads to hospitalization, or persists for >1 week); drug-related toxicity that causes a >2 week delay in Cycle 2 initiation; drug-related toxicity that causes treatment discontinuation or missed dosage of gebasaxturev; or Gr 5 toxicity. The analysis population included all allocated participants in Part 2 who received at least 1 dose of study treatment who met the criteria for DLT evaluability (e.g. finished Cycle 1 without a DLT or experienced a DLT in Cycle 1).
    End point type
    Primary
    End point timeframe
    Cycle 1 (28-day cycle)
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, no statistical analyses were planned for this endpoint.
    End point values
    		 Part 1, Cohort A: Triple-Negative Breast Cancer Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma Part 2 Dose Level 1, Solid Tumors + Liver Metastases Part 2 Dose Level 2, Solid Tumors + Liver Metastases Part 2 Dose Level 3, Solid Tumors + Liver Metastases
    Number of subjects analysed
    0 [6]
    0 [7]
    0 [8]
    6
    3
    14
    Units: Participants
    1
    0
    1
    Notes
    [6] - Per protocol, only the participants in Part 2 were analyzed in this outcome measure.
    [7] - Per protocol, only the participants in Part 2 were analyzed in this outcome measure.
    [8] - Per protocol, only the participants in Part 2 were analyzed in this outcome measure.
    No statistical analyses for this end point

    Primary: Part 2: Number of Participants Who Experienced One or More Adverse Events (AEs)

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    End point title
    		 Part 2: Number of Participants Who Experienced One or More Adverse Events (AEs) [9]
    End point description
    An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The analysis population included all allocated participants in Part 2 who received study intervention.
    End point type
    Primary
    End point timeframe
    Up to approximately 29 months
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, no statistical analyses were planned for this endpoint.
    End point values
    		 Part 1, Cohort A: Triple-Negative Breast Cancer Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma Part 2 Dose Level 1, Solid Tumors + Liver Metastases Part 2 Dose Level 2, Solid Tumors + Liver Metastases Part 2 Dose Level 3, Solid Tumors + Liver Metastases
    Number of subjects analysed
    0 [10]
    0 [11]
    0 [12]
    6
    3
    14
    Units: Participants
    6
    2
    14
    Notes
    [10] - Per protocol, only participants in Part 2 were analyzed in this outcome measure.
    [11] - Per protocol, only participants in Part 2 were analyzed in this outcome measure.
    [12] - Per protocol, only participants in Part 2 were analyzed in this outcome measure.
    No statistical analyses for this end point

    Primary: Part 2: Number of Participants Who Discontinued Study Intervention Due to an AE

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    End point title
    		 Part 2: Number of Participants Who Discontinued Study Intervention Due to an AE [13]
    End point description
    An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The analysis population included all allocated participants in Part 2 who received study intervention.
    End point type
    Primary
    End point timeframe
    Up to approximately 10 months
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, no statistical analyses were planned for this endpoint.
    End point values
    		 Part 1, Cohort A: Triple-Negative Breast Cancer Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma Part 2 Dose Level 1, Solid Tumors + Liver Metastases Part 2 Dose Level 2, Solid Tumors + Liver Metastases Part 2 Dose Level 3, Solid Tumors + Liver Metastases
    Number of subjects analysed
    0 [14]
    0 [15]
    0 [16]
    6
    3
    14
    Units: Participants
    0
    0
    1
    Notes
    [14] - Per protocol, only participants in Part 2 were analyzed in this outcome measure
    [15] - Per protocol, only participants in Part 2 were analyzed in this outcome measure
    [16] - Per protocol, only participants in Part 2 were analyzed in this outcome measure
    No statistical analyses for this end point

    Secondary: Part 1: Number of Participants Who Experienced One or More AEs

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    End point title
    		 Part 1: Number of Participants Who Experienced One or More AEs
    End point description
    An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The analysis population included all allocated participants in Part 1 who received study intervention.
    End point type
    Secondary
    End point timeframe
    Up to approximately 30 months
    End point values
    		 Part 1, Cohort A: Triple-Negative Breast Cancer Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma Part 2 Dose Level 1, Solid Tumors + Liver Metastases Part 2 Dose Level 2, Solid Tumors + Liver Metastases Part 2 Dose Level 3, Solid Tumors + Liver Metastases
    Number of subjects analysed
    21
    14
    17
    0 [17]
    0 [18]
    0 [19]
    Units: Participants
    19
    14
    17
    Notes
    [17] - Per protocol, only participants in Part 1 were analyzed in this outcome measure.
    [18] - Per protocol, only participants in Part 1 were analyzed in this outcome measure.
    [19] - Per protocol, only participants in Part 1 were analyzed in this outcome measure.
    No statistical analyses for this end point

    Secondary: Part 1: Number of Participants Who Discontinued Study Intervention Due to an AE

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    End point title
    		 Part 1: Number of Participants Who Discontinued Study Intervention Due to an AE
    End point description
    An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The analysis population included all allocated participants in Part 1 who received study intervention.
    End point type
    Secondary
    End point timeframe
    Up to approximately 23 months
    End point values
    		 Part 1, Cohort A: Triple-Negative Breast Cancer Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma Part 2 Dose Level 1, Solid Tumors + Liver Metastases Part 2 Dose Level 2, Solid Tumors + Liver Metastases Part 2 Dose Level 3, Solid Tumors + Liver Metastases
    Number of subjects analysed
    21
    14
    17
    0 [20]
    0 [21]
    0 [22]
    Units: Participants
    1
    3
    3
    Notes
    [20] - Per protocol, only participants in Part 1 were analyzed in this outcome measure
    [21] - Per protocol, only participants in Part 1 were analyzed in this outcome measure
    [22] - Per protocol, only participants in Part 1 were analyzed in this outcome measure
    No statistical analyses for this end point

    Secondary: Progression-Free Survival (PFS) per RECIST 1.1 as Assessed by Investigator

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    End point title
    		 Progression-Free Survival (PFS) per RECIST 1.1 as Assessed by Investigator
    End point description
    PFS was defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by investigator. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection does not render a lesion non-evaluable. A value of 9999 indicates that the upper limit not reached at time of data cut-off due to insufficient number of participants with an event. The analysis population consisted of all allocated participants in Part 1 with a baseline scan that demonstrated measurable disease and who received at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Up to approximately 30 months
    End point values
    		 Part 1, Cohort A: Triple-Negative Breast Cancer Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma Part 2 Dose Level 1, Solid Tumors + Liver Metastases Part 2 Dose Level 2, Solid Tumors + Liver Metastases Part 2 Dose Level 3, Solid Tumors + Liver Metastases
    Number of subjects analysed
    21
    14
    17
    0 [23]
    0 [24]
    0 [25]
    Units: Months
        median (confidence interval 95%)
    2.1 (1.5 to 3.1)
    3.3 (1.7 to 9999)
    15.4 (2.4 to 9999)
    ( to )
    ( to )
    ( to )
    Notes
    [23] - Per protocol, only participants in Part 1 were analyzed in this outcome measure.
    [24] - Per protocol, only participants in Part 1 were analyzed in this outcome measure.
    [25] - Per protocol, only participants in Part 1 were analyzed in this outcome measure.
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR) per RECIST 1.1 as Assessed by Investigator

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    End point title
    		 Duration of Response (DOR) per RECIST 1.1 as Assessed by Investigator
    End point description
    For participants who demonstrated a confirmed immune-based Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by investigator, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. For this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection did not render a lesion non-evaluable. A value of 9999 indicates that the median and upper limit were not reached at time of data cut-off due to insufficient number of responding participants with relapse. The analysis population consisted of all allocated participants in Part 1 who experienced a confirmed CR or PR with a baseline scan that demonstrated measurable disease and who received at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Up to approximately 30 months
    End point values
    		 Part 1, Cohort A: Triple-Negative Breast Cancer Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma Part 2 Dose Level 1, Solid Tumors + Liver Metastases Part 2 Dose Level 2, Solid Tumors + Liver Metastases Part 2 Dose Level 3, Solid Tumors + Liver Metastases
    Number of subjects analysed
    0 [26]
    5
    11
    0 [27]
    0 [28]
    0 [29]
    Units: Months
        median (confidence interval 95%)
    ( to )
    9999 (4.4 to 9999)
    9999 (4.6 to 9999)
    ( to )
    ( to )
    ( to )
    Notes
    [26] - No participants in Part 1, Cohort A were eligible for analysis.
    [27] - Per protocol, only participants in Part 1 were analyzed in this outcome measure.
    [28] - Per protocol, only participants in Part 1 were analyzed in this outcome measure.
    [29] - Per protocol, only participants in Part 1 were analyzed in this outcome measure.
    No statistical analyses for this end point

    Secondary: PFS per Response Evaluation Criteria in Solid Tumors 1.1 for Immune-Based Therapeutics (iRECIST) as Assessed by Investigator

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    End point title
    		 PFS per Response Evaluation Criteria in Solid Tumors 1.1 for Immune-Based Therapeutics (iRECIST) as Assessed by Investigator
    End point description
    PFS was defined as the time from first dose of study treatment to the first documented immune-based confirmed progressive disease (iCPD) or death due to any cause, whichever occurs first as assessed by investigator. Per iRECIST, iCPD was defined as worsening of any existing cause of progression, or the appearance of any other cause of progression, relative to the initial appearance of progressive disease by RECIST 1.1. A value of 9999 indicates that the upper limit not reached at time of data cut-off due to insufficient number of participants with an event. The analysis population consisted of all allocated participants in Part 1 with a baseline scan that demonstrated measurable disease and who received at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Up to approximately 30 months
    End point values
    		 Part 1, Cohort A: Triple-Negative Breast Cancer Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma Part 2 Dose Level 1, Solid Tumors + Liver Metastases Part 2 Dose Level 2, Solid Tumors + Liver Metastases Part 2 Dose Level 3, Solid Tumors + Liver Metastases
    Number of subjects analysed
    21
    14
    17
    0 [30]
    0 [31]
    0 [32]
    Units: Months
        median (confidence interval 95%)
    3.3 (1.3 to 4.3)
    8.2 (2.1 to 9999)
    20.4 (3.3 to 9999)
    ( to )
    ( to )
    ( to )
    Notes
    [30] - Per protocol, only participants in Part 1 were analyzed in this outcome measure.
    [31] - Per protocol, only participants in Part 1 were analyzed in this outcome measure.
    [32] - Per protocol, only participants in Part 1 were analyzed in this outcome measure.
    No statistical analyses for this end point

    Secondary: DOR per iRECIST as Assessed by Investigator

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    End point title
    		 DOR per iRECIST as Assessed by Investigator
    End point description
    For participants who demonstrated confirmed CR (disappearance of all target lesions and non-target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 or immune-based Complete Response (iCR: Disappearance of all target lesions) or immune-based Partial Response (iPR: ≥30% decrease in the sum of diameters of target lesions) after a single PD per iRECIST, DOR was defined as the time from the first documented CR or PR, or iCR or an iPR, as assessed by investigator, until progressive disease or death, whichever occurs first. A value of 9999 indicates that the median and upper limit were not reached at time of data cut-off due to insufficient number of responding participants with relapse. The analysis population consisted of all allocated participants in Part 1 who experienced a confirmed response (CR, PR, iCR or iPR) with a baseline scan that demonstrated measurable disease and who received at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Up to approximately 30 months
    End point values
    		 Part 1, Cohort A: Triple-Negative Breast Cancer Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma Part 2 Dose Level 1, Solid Tumors + Liver Metastases Part 2 Dose Level 2, Solid Tumors + Liver Metastases Part 2 Dose Level 3, Solid Tumors + Liver Metastases
    Number of subjects analysed
    0 [33]
    6
    11
    0 [34]
    0 [35]
    0 [36]
    Units: Months
        median (confidence interval 95%)
    ( to )
    9999 (4.4 to 9999)
    9999 (4.6 to 9999)
    ( to )
    ( to )
    ( to )
    Notes
    [33] - No participants in Part 1, Cohort A were eligible for analysis.
    [34] - Per protocol, only participants in Part 1 were analyzed in this outcome measure.
    [35] - Per protocol, only participants in Part 1 were analyzed in this outcome measure.
    [36] - Per protocol, only participants in Part 1 were analyzed in this outcome measure.
    No statistical analyses for this end point

    Secondary: ORR per iRECIST as Assessed by Investigator

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    End point title
    		 ORR per iRECIST as Assessed by Investigator
    End point description
    ORR was defined as the percentage of participants who had confirmed responses assessed using RECIST 1.1 before PD or an immune-based Complete Response (iCR: Disappearance of all target lesions) or an immune-based Partial Response (iPR: ≥30% decrease in the sum of diameters of target lesions) after a single PD per iRECIST as assessed by investigator. The analysis population consisted of all participants with a baseline scan that demonstrated measurable disease and who were administered at least one dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Up to approximately 30 months
    End point values
    		 Part 1, Cohort A: Triple-Negative Breast Cancer Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma Part 2 Dose Level 1, Solid Tumors + Liver Metastases Part 2 Dose Level 2, Solid Tumors + Liver Metastases Part 2 Dose Level 3, Solid Tumors + Liver Metastases
    Number of subjects analysed
    21
    14
    17
    6
    3
    14
    Units: Percentage of Participants
        number (confidence interval 95%)
    0.0 (0.0 to 16.1)
    42.9 (17.7 to 71.1)
    64.7 (38.3 to 85.8)
    16.7 (0.4 to 64.1)
    0.0 (0.0 to 70.8)
    0.0 (0.0 to 23.2)
    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 dose of study intervention to death due to any cause. The analysis population consisted of all allocated participants in Part 1 with a baseline scan that demonstrated measurable disease and who received at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Up to approximately 30 months
    End point values
    		 Part 1, Cohort A: Triple-Negative Breast Cancer Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma Part 2 Dose Level 1, Solid Tumors + Liver Metastases Part 2 Dose Level 2, Solid Tumors + Liver Metastases Part 2 Dose Level 3, Solid Tumors + Liver Metastases
    Number of subjects analysed
    21
    14
    17
    0 [37]
    0 [38]
    0 [39]
    Units: Months
        median (confidence interval 95%)
    7.5 (4.3 to 15.0)
    11.8 (3.0 to 9999)
    20.4 (3.3 to 9999)
    ( to )
    ( to )
    ( to )
    Notes
    [37] - Per protocol, only participants in Part 1 were analyzed in this outcome measure
    [38] - Per protocol, only participants in Part 1 were analyzed in this outcome measure
    [39] - Per protocol, only participants in Part 1 were analyzed in this outcome measure
    No statistical analyses for this end point

    Secondary: Part 2: ORR per RECIST 1.1 as Assessed by Investigator

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    End point title
    		 Part 2: ORR per RECIST 1.1 as Assessed by Investigator
    End point description
    ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions and no new lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by investigator. For this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection does not render a lesion non-evaluable. The analysis population consisted of all allocated participants in Part 2 with a baseline scan that demonstrated measurable disease and who received at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Up to approximately 29 months
    End point values
    		 Part 1, Cohort A: Triple-Negative Breast Cancer Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma Part 2 Dose Level 1, Solid Tumors + Liver Metastases Part 2 Dose Level 2, Solid Tumors + Liver Metastases Part 2 Dose Level 3, Solid Tumors + Liver Metastases
    Number of subjects analysed
    0 [40]
    0 [41]
    0 [42]
    6
    3
    14
    Units: Percentage of Participants
        number (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    16.7 (0.4 to 64.1)
    0.0 (0.0 to 70.8)
    0.0 (0.0 to 23.2)
    Notes
    [40] - Per protocol, only participants in Part 2 were analyzed for this outcome measure.
    [41] - Per protocol, only participants in Part 2 were analyzed for this outcome measure.
    [42] - Per protocol, only participants in Part 2 were analyzed for this outcome measure.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to approximately 30 months
    Adverse event reporting additional description
    Deaths (all-causes) includes all allocated participants. Serious and Other AE tables include all allocated participants who received at least 1 dose of study drug. Per protocol, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to drug were excluded as AEs.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Part 1, Cohort A: Triple-Negative Breast Cancer
    Reporting group description
    		 Participants with triple-negative breast cancer (TNBC) solid tumors received 3 X 10^8 50% tissue culture infectious dose (TCID50) of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.

    Reporting group title
    Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma
    Reporting group description
    		 Participants with head and neck squamous cell carcinoma (HNSCC) solid tumors received 3 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.

    Reporting group title
    Part 2 Dose Level 3, Solid Tumors + Liver Metastases
    Reporting group description
    		 Participants with solid tumors with liver metastases received 3 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.

    Reporting group title
    Part 2 Dose Level 1, Solid Tumors + Liver Metastases
    Reporting group description
    		 Participants with solid tumors with liver metastases received 3 X 10^7 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.

    Reporting group title
    Part 2 Dose Level 2, Solid Tumors + Liver Metastases
    Reporting group description
    		 Participants with solid tumors with liver metastases received 1 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.

    Reporting group title
    Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma
    Reporting group description
    		 Participants with cutaneous squamous cell carcinoma (cSCC) solid tumors received 3 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 was 28 days, and cycles 2-35 were 21 days.

    Serious adverse events
    		 Part 1, Cohort A: Triple-Negative Breast Cancer Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma Part 2 Dose Level 3, Solid Tumors + Liver Metastases Part 2 Dose Level 1, Solid Tumors + Liver Metastases Part 2 Dose Level 2, Solid Tumors + Liver Metastases Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 21 (19.05%)
    8 / 14 (57.14%)
    3 / 14 (21.43%)
    4 / 6 (66.67%)
    1 / 3 (33.33%)
    6 / 17 (35.29%)
         number of deaths (all causes)
    18
    8
    7
    5
    2
    8
         number of deaths resulting from adverse events
    0
    0
    1
    0
    0
    3
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Infected neoplasm
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tumour haemorrhage
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Troponin increased
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Cervical vertebral fracture
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic seroma
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Cardiac failure congestive
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Polyneuropathy
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    General physical health deterioration
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Pain
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholestasis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 14 (14.29%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    2 / 21 (9.52%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract haemorrhage
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Stevens-Johnson syndrome
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lichenoid keratosis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 14 (14.29%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Part 1, Cohort A: Triple-Negative Breast Cancer Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma Part 2 Dose Level 3, Solid Tumors + Liver Metastases Part 2 Dose Level 1, Solid Tumors + Liver Metastases Part 2 Dose Level 2, Solid Tumors + Liver Metastases Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    18 / 21 (85.71%)
    14 / 14 (100.00%)
    14 / 14 (100.00%)
    6 / 6 (100.00%)
    2 / 3 (66.67%)
    17 / 17 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 14 (14.29%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    Haemangioma of spleen
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Melanocytic naevus
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Tumour pain
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    3 / 17 (17.65%)
         occurrences all number
    1
    1
    0
    0
    0
    3
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Embolism
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Hypertension
         subjects affected / exposed
    2 / 21 (9.52%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    2
    0
    1
    1
    0
    1
    General disorders and administration site conditions
    Influenza like illness
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    5
    0
    0
    0
    Fatigue
         subjects affected / exposed
    2 / 21 (9.52%)
    3 / 14 (21.43%)
    4 / 14 (28.57%)
    3 / 6 (50.00%)
    0 / 3 (0.00%)
    4 / 17 (23.53%)
         occurrences all number
    8
    3
    5
    3
    0
    4
    Facial pain
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Face oedema
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Discomfort
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Chills
         subjects affected / exposed
    4 / 21 (19.05%)
    1 / 14 (7.14%)
    1 / 14 (7.14%)
    3 / 6 (50.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    6
    1
    1
    3
    0
    1
    Asthenia
         subjects affected / exposed
    2 / 21 (9.52%)
    1 / 14 (7.14%)
    3 / 14 (21.43%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    4 / 17 (23.53%)
         occurrences all number
    2
    1
    5
    0
    0
    4
    Injection site bruising
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Pyrexia
         subjects affected / exposed
    6 / 21 (28.57%)
    1 / 14 (7.14%)
    5 / 14 (35.71%)
    2 / 6 (33.33%)
    1 / 3 (33.33%)
    2 / 17 (11.76%)
         occurrences all number
    10
    2
    8
    2
    1
    2
    Pain
         subjects affected / exposed
    4 / 21 (19.05%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    4
    0
    0
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Oedema
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Swelling face
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Injection site pruritus
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    2
    0
    0
    0
    0
    1
    Injection site pain
         subjects affected / exposed
    2 / 21 (9.52%)
    1 / 14 (7.14%)
    2 / 14 (14.29%)
    2 / 6 (33.33%)
    0 / 3 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    5
    2
    5
    3
    0
    2
    Injection site oedema
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Injection site inflammation
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Injection site erythema
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Mucosal inflammation
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Reproductive system and breast disorders
    Breast pain
         subjects affected / exposed
    4 / 21 (19.05%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    4
    0
    0
    0
    0
    0
    Pelvic discomfort
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Perineal pain
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Hiccups
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Cough
         subjects affected / exposed
    5 / 21 (23.81%)
    1 / 14 (7.14%)
    2 / 14 (14.29%)
    2 / 6 (33.33%)
    0 / 3 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    5
    1
    2
    2
    0
    2
    Dyspnoea
         subjects affected / exposed
    3 / 21 (14.29%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    3
    0
    0
    0
    0
    1
    Dyspnoea exertional
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Epistaxis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Haemoptysis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Lower respiratory tract congestion
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Orthopnoea
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Productive cough
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Rhinorrhoea
         subjects affected / exposed
    0 / 21 (0.00%)
    3 / 14 (21.43%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    0
    Stridor
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    1
    0
    0
    0
    0
    2
    Confusional state
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Depression
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Hallucination, visual
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Insomnia
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 14 (14.29%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 21 (19.05%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    4
    0
    1
    0
    0
    2
    Amylase increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    1
    0
    1
    2
    Aspartate aminotransferase increased
         subjects affected / exposed
    4 / 21 (19.05%)
    0 / 14 (0.00%)
    3 / 14 (21.43%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    3 / 17 (17.65%)
         occurrences all number
    4
    0
    3
    0
    0
    3
    Bilirubin conjugated increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    2 / 14 (14.29%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    2
    0
    0
    0
    Blood creatine increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Blood creatine phosphokinase increased
         subjects affected / exposed
    3 / 21 (14.29%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    3
    0
    0
    0
    0
    1
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Blood urea increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    C-reactive protein increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    CD4 lymphocytes increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    2 / 21 (9.52%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    1
    0
    0
    0
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Neutrophil count increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Platelet count decreased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Thyroxine free increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Thyroxine increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Troponin T increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Weight decreased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    White blood cell count decreased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Protein total decreased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Injury, poisoning and procedural complications
    Skin wound
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Skin abrasion
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Nasal injury
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Limb injury
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Fibula fracture
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Stoma complication
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Arthropod sting
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Spinal compression fracture
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Fall
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Sinus tachycardia
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Bradycardia
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    Atrial fibrillation
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    Angina pectoris
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    2 / 14 (14.29%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    1
    2
    0
    0
    0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Encephalopathy
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Headache
         subjects affected / exposed
    2 / 21 (9.52%)
    2 / 14 (14.29%)
    3 / 14 (21.43%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    4 / 17 (23.53%)
         occurrences all number
    6
    2
    4
    2
    0
    5
    Hypoaesthesia
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Neuropathy peripheral
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    1
    0
    0
    0
    0
    2
    Post herpetic neuralgia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Somnolence
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    3 / 14 (21.43%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 21 (23.81%)
    0 / 14 (0.00%)
    2 / 14 (14.29%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    5
    0
    3
    1
    0
    1
    Hyperleukocytosis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Thrombocytopenia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Lymphopenia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Ear and labyrinth disorders
    Ear discomfort
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Deafness
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Eye disorders
    Vision blurred
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Exophthalmos
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Dry eye
         subjects affected / exposed
    2 / 21 (9.52%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Lacrimation increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Gastrointestinal disorders
    Anorectal discomfort
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Abdominal pain lower
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Abdominal pain
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    3 / 14 (21.43%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    2
    1
    3
    0
    0
    0
    Ascites
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Constipation
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    2 / 14 (14.29%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    2
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    3 / 14 (21.43%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    4 / 17 (23.53%)
         occurrences all number
    0
    2
    3
    0
    0
    12
    Dry mouth
         subjects affected / exposed
    2 / 21 (9.52%)
    1 / 14 (7.14%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    2
    1
    1
    0
    0
    0
    Dysphagia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Epigastric discomfort
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Eructation
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    Nausea
         subjects affected / exposed
    5 / 21 (23.81%)
    2 / 14 (14.29%)
    5 / 14 (35.71%)
    1 / 6 (16.67%)
    1 / 3 (33.33%)
    0 / 17 (0.00%)
         occurrences all number
    8
    2
    9
    2
    1
    0
    Odynophagia
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Oral pain
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Salivary gland pain
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Stomatitis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Vomiting
         subjects affected / exposed
    3 / 21 (14.29%)
    0 / 14 (0.00%)
    4 / 14 (28.57%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    3
    0
    9
    0
    0
    1
    Toothache
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Tongue geographic
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Hyperhidrosis
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Acne
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Actinic keratosis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Blister
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Dermatitis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Dermatitis bullous
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Night sweats
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Pruritus
         subjects affected / exposed
    1 / 21 (4.76%)
    4 / 14 (28.57%)
    0 / 14 (0.00%)
    1 / 6 (16.67%)
    1 / 3 (33.33%)
    2 / 17 (11.76%)
         occurrences all number
    1
    4
    0
    1
    1
    2
    Rash
         subjects affected / exposed
    1 / 21 (4.76%)
    3 / 14 (21.43%)
    3 / 14 (21.43%)
    1 / 6 (16.67%)
    1 / 3 (33.33%)
    1 / 17 (5.88%)
         occurrences all number
    1
    4
    3
    2
    1
    1
    Rash macular
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Skin haemorrhage
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Vitiligo
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Skin erosion
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Renal and urinary disorders
    Chronic kidney disease
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Nocturia
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Pollakiuria
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Thyroiditis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Hypothyroidism
         subjects affected / exposed
    4 / 21 (19.05%)
    6 / 14 (42.86%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    4
    6
    0
    0
    0
    0
    Hyperthyroidism
         subjects affected / exposed
    5 / 21 (23.81%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    5
    1
    0
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Muscle spasms
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    3
    1
    0
    0
    0
    0
    Arthralgia
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    4 / 14 (28.57%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    4 / 17 (23.53%)
         occurrences all number
    0
    2
    5
    0
    0
    4
    Back pain
         subjects affected / exposed
    2 / 21 (9.52%)
    1 / 14 (7.14%)
    3 / 14 (21.43%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    2
    1
    3
    0
    0
    1
    Bone pain
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Flank pain
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    2 / 21 (9.52%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Myalgia
         subjects affected / exposed
    2 / 21 (9.52%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    3
    0
    4
    0
    0
    1
    Neck pain
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Skin infection
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    Rhinitis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Respiratory tract infection
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Pneumonia aspiration
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Pneumonia
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 14 (14.29%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    Oral candidiasis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Myiasis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Influenza
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Herpes zoster
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Gingivitis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    COVID-19
         subjects affected / exposed
    0 / 21 (0.00%)
    5 / 14 (35.71%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    4 / 17 (23.53%)
         occurrences all number
    0
    5
    0
    0
    0
    4
    Viral infection
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    2 / 21 (9.52%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    2
    0
    1
    0
    0
    3
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    2 / 14 (14.29%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    4 / 17 (23.53%)
         occurrences all number
    1
    0
    2
    1
    0
    4
    Hypercalcaemia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Hyperkalaemia
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 14 (14.29%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    1
    0
    2
    Hypokalaemia
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    2
    0
    0
    0
    0
    Hypomagnesaemia
         subjects affected / exposed
    2 / 21 (9.52%)
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    2
    0
    0
    0
    0
    1
    Hypophosphataemia
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    1
    1
    0
    1
    0
    1
    Hyponatraemia
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    3
    1
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Jul 2020
    The main purpose of AM1 was to add the IND number.
    27 Jan 2021
    The main purpose of AM2 was to clarify existing language, provide country specific requirements, and to remove sections that were not applicable to the study.
    04 Jun 2021
    The main purpose of AM3 was to address agency feedback and provide updated language to the pembrolizumab dose modification portion of the study.
    02 Feb 2023
    The main purpose of AM4 was to allow ongoing participants to transfer to another sponsored protocol to continue receiving pembrolizumab, incorporate previously released Protocol Clarification Letters, and update the Sponsor corporate name.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    25 Jul 2023
    This study was terminated due to business reasons.
    -

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

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