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    Clinical Trial Results:
    A Phase 2, Randomized Clinical Study of Intravenous or Intratumoral Administration of V937 in Combination with Pembrolizumab (MK-3475) Versus Pembrolizumab Alone in Participants with Advanced/Metastatic Melanoma

    Summary
    EudraCT number
    		 2019-002034-36
    Trial protocol
    		 NO   GB   ES   FR   DE   IT  
    Global end of trial date
    12 Jul 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    03 Jul 2024
    First version publication date
    03 Jul 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    V937-011
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04152863
    WHO universal trial number (UTN)
    		 -
    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@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@merck.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
    12 Jul 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    12 Jul 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Jul 2023
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate the objective response rate (ORR) of participants treated with IV V937 administered in combination with pembrolizumab, ITu V937 administered in combination with pembrolizumab, or pembrolizumab alone per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).
    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
    05 Jun 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
    Australia: 6
    Country: Number of subjects enrolled
    Chile: 10
    Country: Number of subjects enrolled
    Germany: 7
    Country: Number of subjects enrolled
    Spain: 4
    Country: Number of subjects enrolled
    France: 2
    Country: Number of subjects enrolled
    Israel: 5
    Country: Number of subjects enrolled
    Italy: 2
    Country: Number of subjects enrolled
    Korea, Republic of: 3
    Country: Number of subjects enrolled
    Norway: 2
    Country: Number of subjects enrolled
    United States: 1
    Country: Number of subjects enrolled
    South Africa: 43
    Worldwide total number of subjects
    85
    EEA total number of subjects
    17
    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)
    52
    From 65 to 84 years
    30
    85 years and over
    3

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Screening procedures completed within 28 days prior to treatment initiation, exceptions included were laboratory tests, evaluation of Eastern Cooperative Oncology Group, a urine or serum pregnancy test for women of childbearing potential within 72 hours; newly obtained tumor tissue was obtained within 90 days of treatment initiation.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Intravenous (IV) Gebasaxturev + IV Pembrolizumab
    Arm description
    		 Participants received gebasaxturev at a dose of 1 X 10^9 50% tissue culture infectious dose (TCID50) by IV infusion on Days 1, 3, 5, and 8 of Cycle 1 (28-day cycle) and Day 1 of Cycles 2-8 (21-day cycles) plus pembrolizumab 200 mg by IV infusion on Day 8 of Cycle 1 (28-day cycle) and Day 1 of each subsequent 21-day cycle. Gebasaxturev was administered for up to 8 cycles (up to 6 months). Pembrolizumab was administered for up to 35 cycles (up to 2 years).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Gebasaxturev IV
    Investigational medicinal product code
    Other name
    Coxsackievirus A21 (CVA21) Formerly known as CAVATAK® CAV21 V937
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered as an IV infusion of 1 X 10^9 TCID50

    Arm title
    		 Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab
    Arm description
    		 Participants received gebasaxturev at a dose of 3 X 10^8 TCID50 by ITu injection on Days 1, 3, 5, and 8 of Cycle 1 (28-day cycle) and Day 1 of Cycles 2-8 (21-day cycles) plus pembrolizumab 200 mg by IV infusion on Day 8 of Cycle 1 (28-day cycle) and Day 1 of each subsequent 21-day cycle. Gebasaxturev was administered for up to 8 cycles (up to 6 months). Pembrolizumab was administered for up to 35 cycles (up to 2 years).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Gebasaxturev ITu
    Investigational medicinal product code
    Other name
    Coxsackievirus A21 (CVA21) Formerly known as CAVATAK® CAV21 V937
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intratumoral use
    Dosage and administration details
    Administered as an ITu injection of 3 X 10^8 TCID50

    Arm title
    		 Pembrolizumab IV
    Arm description
    		 Participants received pembrolizumab 200 mg by IV infusion on Day 8 of Cycle 1 (28-day cycle) and Day 1 of each subsequent 21-day cycle. Pembrolizumab was administered for up to 35 cycles (up to 2 years).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475 Keytruda®
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered as an IV infusion of 200 mg

    Number of subjects in period 1
    		Intravenous (IV) Gebasaxturev + IV Pembrolizumab Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab Pembrolizumab IV
    Started
    28
    28
    29
    Completed
    0
    0
    0
    Not completed
    28
    28
    29
         Physician decision
    1
    1
    1
         Consent withdrawn by subject
    2
    1
    3
         Death
    13
    12
    7
         Participation in Study Terminated by Sponsor
    12
    14
    18

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Intravenous (IV) Gebasaxturev + IV Pembrolizumab
    Reporting group description
    		 Participants received gebasaxturev at a dose of 1 X 10^9 50% tissue culture infectious dose (TCID50) by IV infusion on Days 1, 3, 5, and 8 of Cycle 1 (28-day cycle) and Day 1 of Cycles 2-8 (21-day cycles) plus pembrolizumab 200 mg by IV infusion on Day 8 of Cycle 1 (28-day cycle) and Day 1 of each subsequent 21-day cycle. Gebasaxturev was administered for up to 8 cycles (up to 6 months). Pembrolizumab was administered for up to 35 cycles (up to 2 years).

    Reporting group title
    Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab
    Reporting group description
    		 Participants received gebasaxturev at a dose of 3 X 10^8 TCID50 by ITu injection on Days 1, 3, 5, and 8 of Cycle 1 (28-day cycle) and Day 1 of Cycles 2-8 (21-day cycles) plus pembrolizumab 200 mg by IV infusion on Day 8 of Cycle 1 (28-day cycle) and Day 1 of each subsequent 21-day cycle. Gebasaxturev was administered for up to 8 cycles (up to 6 months). Pembrolizumab was administered for up to 35 cycles (up to 2 years).

    Reporting group title
    Pembrolizumab IV
    Reporting group description
    		 Participants received pembrolizumab 200 mg by IV infusion on Day 8 of Cycle 1 (28-day cycle) and Day 1 of each subsequent 21-day cycle. Pembrolizumab was administered for up to 35 cycles (up to 2 years).

    Reporting group values
    		 Intravenous (IV) Gebasaxturev + IV Pembrolizumab Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab Pembrolizumab IV Total
    Number of subjects
    		 28 28 29 85
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 13 19 20 52
        From 65-84 years
    		 14 8 8 30
        85 years and over
    		 1 1 1 3
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 64.8 ( 10.5 ) 58.3 ( 13.6 ) 60.5 ( 11.9 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 8 10 11 29
        Male
    		 20 18 18 56
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0
        Asian
    		 2 0 1 3
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0
        Black or African American
    		 3 3 2 8
        White
    		 23 24 26 73
        More than one race
    		 0 0 0 0
        Unknown or Not Reported
    		 0 1 0 1
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 2 6 3 11
        Not Hispanic or Latino
    		 25 21 26 72
        Unknown or Not Reported
    		 1 1 0 2
    Cancer M Staging at Baseline
    A study specific characteristic, randomization was stratified based on 4 metastatic melanoma subsets: M1a (nonvisceral (distant cutaneous, subcutaneous, nodal); M1b (lung); M1c (noncentral nervous system (CNS) visceral); and M1d (involves the CNS),as defined by the AJCC (American Joint Committee on Cancer) Cancer Staging Manual, Eighth Edition. M1c and M1d have different prognoses compared to M1a and M1b, warranting stratification.
    Units: Subjects
        M1a
    		 7 9 9 25
        M1b
    		 6 3 5 14
        M1c
    		 12 14 9 35
        M1d
    		 1 1 1 3
        Missing
    		 2 1 5 8

    End points

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    End points reporting groups
    Reporting group title
    Intravenous (IV) Gebasaxturev + IV Pembrolizumab
    Reporting group description
    		 Participants received gebasaxturev at a dose of 1 X 10^9 50% tissue culture infectious dose (TCID50) by IV infusion on Days 1, 3, 5, and 8 of Cycle 1 (28-day cycle) and Day 1 of Cycles 2-8 (21-day cycles) plus pembrolizumab 200 mg by IV infusion on Day 8 of Cycle 1 (28-day cycle) and Day 1 of each subsequent 21-day cycle. Gebasaxturev was administered for up to 8 cycles (up to 6 months). Pembrolizumab was administered for up to 35 cycles (up to 2 years).

    Reporting group title
    Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab
    Reporting group description
    		 Participants received gebasaxturev at a dose of 3 X 10^8 TCID50 by ITu injection on Days 1, 3, 5, and 8 of Cycle 1 (28-day cycle) and Day 1 of Cycles 2-8 (21-day cycles) plus pembrolizumab 200 mg by IV infusion on Day 8 of Cycle 1 (28-day cycle) and Day 1 of each subsequent 21-day cycle. Gebasaxturev was administered for up to 8 cycles (up to 6 months). Pembrolizumab was administered for up to 35 cycles (up to 2 years).

    Reporting group title
    Pembrolizumab IV
    Reporting group description
    		 Participants received pembrolizumab 200 mg by IV infusion on Day 8 of Cycle 1 (28-day cycle) and Day 1 of each subsequent 21-day cycle. Pembrolizumab was administered for up to 35 cycles (up to 2 years).

    Subject analysis set title
    Intravenous (IV) Gebasaxturev + IV Pembrolizumab
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received gebasaxturev at a dose of 1 X 10^9 50% tissue culture infectious dose (TCID50) by IV infusion on Days 1, 3, 5, and 8 of Cycle 1 (28-day cycle) and Day 1 of Cycles 2-8 (21-day cycles) plus pembrolizumab 200 mg by IV infusion on Day 8 of Cycle 1 (28-day cycle) and Day 1 of each subsequent 21-day cycle. Gebasaxturev was administered for up to 8 cycles (up to 6 months). Pembrolizumab was administered for up to 35 cycles (up to 2 years).

    Subject analysis set title
    Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received gebasaxturev at a dose of 3 X 10^8 TCID50 by ITu injection on Days 1, 3, 5, and 8 of Cycle 1 (28-day cycle) and Day 1 of Cycles 2-8 (21-day cycles) plus pembrolizumab 200 mg by IV infusion on Day 8 of Cycle 1 (28-day cycle) and Day 1 of each subsequent 21-day cycle. Gebasaxturev was administered for up to 8 cycles (up to 6 months). Pembrolizumab was administered for up to 35 cycles (up to 2 years).

    Subject analysis set title
    Pembrolizumab IV
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received pembrolizumab 200 mg by IV infusion on Day 8 of Cycle 1 (28-day cycle) and Day 1 of each subsequent 21-day cycle. Pembrolizumab was administered for up to 35 cycles (up to 2 years).

    Primary: Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

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    End point title
    		 Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
    End point description
    ORR is defined as the percentage of participants who have a Complete Response (CR: disappearance of all lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions, without evidence of progression based on non-target or new lesions) as assessed by BICR per RECIST 1.1 which was modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a CR or PR based on modified RECIST 1.1 is presented.
    End point type
    Primary
    End point timeframe
    Up to ~ 35 months
    End point values
    		 Intravenous (IV) Gebasaxturev + IV Pembrolizumab Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab Pembrolizumab IV
    Number of subjects analysed
    28
    28
    29
    Units: Percentage of Participants
        number (confidence interval 90%)
    46.4 (30.1 to 63.4)
    39.3 (23.8 to 56.5)
    34.5 (20.0 to 51.4)
    Statistical analysis title
    		 Percentage Difference in ORR
    Statistical analysis description
    Stratified Miettinen & Nurminen method. To ensure adequate number of participants, strata were combined according to sSAP when one treatment had 0 participants in a particular stratum.
    Comparison groups
    Pembrolizumab IV v Intravenous (IV) Gebasaxturev + IV Pembrolizumab
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1812
    Method
    		 Stratified Miettinen and Nurminen method
    Parameter type
    		 Difference in percentage
    Point estimate
    11.9
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -9.5
         upper limit
    		 32.5
    Statistical analysis title
    		 Percentage Difference in ORR
    Statistical analysis description
    Difference in percentage based on Miettinen & Nurminen method.
    Comparison groups
    Intravenous (IV) Gebasaxturev + IV Pembrolizumab v Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    7.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -14.6
         upper limit
    		 28.2
    Statistical analysis title
    		 Percentage Difference in ORR
    Statistical analysis description
    Stratified Miettinen & Nurminen method. To ensure adequate number of participants, strata were combined according to sSAP when one treatment had 0 participants in a particular stratum.
    Comparison groups
    Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab v Pembrolizumab IV
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3548
    Method
    		 Stratified Miettinen and Nurminen method
    Parameter type
    		 Difference in percentage
    Point estimate
    4.8
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -16.2
         upper limit
    		 25.5

    Secondary: Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

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    End point title
    		 Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
    End point description
    PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was 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. Note: The appearance of one or more new lesions is also considered PD. A value of 9999 indicates that upper limit not reached at time of data cut-off due to insufficient number of participants with an event.
    End point type
    Secondary
    End point timeframe
    Up to ~ 35 months
    End point values
    		 Intravenous (IV) Gebasaxturev + IV Pembrolizumab Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab Pembrolizumab IV
    Number of subjects analysed
    28
    28
    29
    Units: Months
        median (confidence interval 95%)
    12.7 (2.4 to 9999)
    7.3 (2.7 to 9999)
    8.6 (2.4 to 9999)
    Statistical analysis title
    		 PFS Hazard Ratio
    Statistical analysis description
    Based on Cox regression model with Efron’s method of tie handling with treatment as a covariate.
    Comparison groups
    Intravenous (IV) Gebasaxturev + IV Pembrolizumab v Pembrolizumab IV
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 2.27
    Statistical analysis title
    		 PFS Hazard Ratio
    Statistical analysis description
    Based on Cox regression model with Efron’s method of tie handling with treatment as a covariate.
    Comparison groups
    Intravenous (IV) Gebasaxturev + IV Pembrolizumab v Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 2.04
    Statistical analysis title
    		 PFS Hazard Ratio
    Statistical analysis description
    Based on Cox regression model with Efron’s method of tie handling with treatment as a covariate.
    Comparison groups
    Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab v Pembrolizumab IV
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 2.29

    Secondary: Duration of Response (DOR)

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    End point title
    		 Duration of Response (DOR)
    End point description
    DOR is defined as the time from first documented evidence of CR or PR until disease progression or death. A value of 9999 indicates that the median, upper and lower limit not reached at time of data cut-off due to insufficient number of participants with an event.
    End point type
    Secondary
    End point timeframe
    Up to ~ 35 months
    End point values
    		 Intravenous (IV) Gebasaxturev + IV Pembrolizumab Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab Pembrolizumab IV
    Number of subjects analysed
    28
    28
    29
    Units: Months
        median (full range (min-max))
    9999 (9999 to 9999)
    9999 (4.1 to 9999)
    9999 (9999 to 9999)
    No statistical analyses for this end point

    Secondary: Objective Response Rate (ORR) per RECIST 1.1, as Assessed by the Investigator

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    End point title
    		 Objective Response Rate (ORR) per RECIST 1.1, as Assessed by the Investigator
    End point description
    ORR is defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a CR or PR based on modified RECIST 1.1 is presented.
    End point type
    Secondary
    End point timeframe
    Up to ~ 35 months
    End point values
    		 Intravenous (IV) Gebasaxturev + IV Pembrolizumab Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab Pembrolizumab IV
    Number of subjects analysed
    28
    28
    29
    Units: Percentage of Participants
        number (confidence interval 90%)
    39.3 (23.8 to 56.5)
    39.3 (23.8 to 56.5)
    41.4 (25.9 to 58.3)
    Statistical analysis title
    		 Difference in percentage of ORR
    Statistical analysis description
    Based on Stratified Miettinen & Nurminen method.
    Comparison groups
    Intravenous (IV) Gebasaxturev + IV Pembrolizumab v Pembrolizumab IV
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Stratified Miettinen & Nurminen method.
    Parameter type
    		 Difference in percentage
    Point estimate
    -2.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -23.1
         upper limit
    		 19.2
    Statistical analysis title
    		 Difference in % of ORR
    Statistical analysis description
    Difference in percentage based on Miettinen & Nurminen method.
    Comparison groups
    Intravenous (IV) Gebasaxturev + IV Pembrolizumab v Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    0
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -21.2
         upper limit
    		 21.2
    Statistical analysis title
    		 Difference in percentage of ORR
    Statistical analysis description
    Difference in percentage based on Miettinen & Nurminen method.
    Comparison groups
    Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab v Pembrolizumab IV
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    -2.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -23.1
         upper limit
    		 19.2

    Secondary: Progression Free Survival (PFS) RECIST 1.1, as assessed by the investigator

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    End point title
    		 Progression Free Survival (PFS) RECIST 1.1, as assessed by the investigator
    End point description
    PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was 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. Note: The appearance of one or more new lesions is also considered PD. A value of 9999 indicates that upper limit not reached at time of data cut-off due to insufficient number of participants with an event.
    End point type
    Secondary
    End point timeframe
    Up to ~ 35 months
    End point values
    		 Intravenous (IV) Gebasaxturev + IV Pembrolizumab Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab Pembrolizumab IV
    Number of subjects analysed
    28
    28
    29
    Units: Months
        median (confidence interval 95%)
    4.6 (2.4 to 15.3)
    6.5 (2.7 to 9999)
    15.4 (2.4 to 9999)
    Statistical analysis title
    		 PFS Hazard Ratio
    Statistical analysis description
    Based on Cox regression model with Efron’s method of tie handling with treatment as a covariate.
    Comparison groups
    Intravenous (IV) Gebasaxturev + IV Pembrolizumab v Pembrolizumab IV
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 3.02
    Statistical analysis title
    		 PFS Hazard Ratio
    Statistical analysis description
    Based on Cox regression model with Efron’s method of tie handling with treatment as a covariate.
    Comparison groups
    Intravenous (IV) Gebasaxturev + IV Pembrolizumab v Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 2.22
    Statistical analysis title
    		 PFS Hazard Ratio
    Statistical analysis description
    Based on Cox regression model with Efron’s method of tie handling with treatment as a covariate.
    Comparison groups
    Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab v Pembrolizumab IV
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 2.68

    Secondary: Duration of Response (DOR) per RECIST 1.1, as assessed by the investigator

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    End point title
    		 Duration of Response (DOR) per RECIST 1.1, as assessed by the investigator
    End point description
    DOR is defined as the time from first documented evidence of CR or PR until disease progression or death. A value of 9999 indicates that the median, upper and lower limit not reached at time of data cut-off due to insufficient number of participants with an event.
    End point type
    Secondary
    End point timeframe
    Up to ~ 35 months
    End point values
    		 Intravenous (IV) Gebasaxturev + IV Pembrolizumab Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab Pembrolizumab IV
    Number of subjects analysed
    28
    28
    29
    Units: Months
        median (full range (min-max))
    9999 (7.1 to 9999)
    9999 (9999 to 9999)
    9999 (8.4 to 9999)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    OS is the time from randomization to death due to any cause. A value of 9999 indicates that upper limit not reached at time of data cut-off due to insufficient number of participants with an event.
    End point type
    Secondary
    End point timeframe
    Up to ~ 35 months
    End point values
    		 Intravenous (IV) Gebasaxturev + IV Pembrolizumab Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab Pembrolizumab IV
    Number of subjects analysed
    28
    28
    29
    Units: Months
        median (confidence interval 95%)
    17.5 (6.8 to 9999)
    24.1 (11.4 to 9999)
    9999 (14.0 to 9999)
    Statistical analysis title
    		 OS Hazard Ratio
    Statistical analysis description
    Based on Cox regression model with Efron’s method of tie handling with treatment as a covariate.
    Comparison groups
    Intravenous (IV) Gebasaxturev + IV Pembrolizumab v Pembrolizumab IV
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 3.79
    Statistical analysis title
    		 OS Hazard Ratio
    Statistical analysis description
    Based on Cox regression model with Efron’s method of tie handling with treatment as a covariate.
    Comparison groups
    Intravenous (IV) Gebasaxturev + IV Pembrolizumab v Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 3.02
    Statistical analysis title
    		 OS Hazard Ratio
    Statistical analysis description
    Based on Cox regression model with Efron’s method of tie handling with treatment as a covariate.
    Comparison groups
    Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab v Pembrolizumab IV
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 2.68

    Secondary: Percentage of Participants Who Experienced an Adverse Event (AE)

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    End point title
    		 Percentage of Participants Who Experienced an Adverse Event (AE)
    End point description
    An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
    End point type
    Secondary
    End point timeframe
    Up to ~ 37 months
    End point values
    		 Intravenous (IV) Gebasaxturev + IV Pembrolizumab Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab Pembrolizumab IV
    Number of subjects analysed
    28
    28
    26
    Units: Percentage of Participants
        number (not applicable)
    100
    100
    84.6
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Discontinued Study Drug Due to an AE

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    End point title
    		 Percentage of Participants Who Discontinued Study Drug Due to an AE
    End point description
    An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
    End point type
    Secondary
    End point timeframe
    Up to ~ 27 months
    End point values
    		 Intravenous (IV) Gebasaxturev + IV Pembrolizumab Intratumoral (ITu) Gebasaxturev + IV Pembrolizumab Pembrolizumab IV
    Number of subjects analysed
    28
    28
    26
    Units: Percentage of Participants
        number (not applicable)
    14.3
    7.1
    3.8
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to ~ 37 months
    Adverse event reporting additional description
    All-cause mortality (ACM) was analyzed in all randomized participants. Safety analyses were conducted in all randomized participants who received at least 1 dose of study intervention. Per protocol, MedDRA terms "Neoplasm progression (NP)", "Malignant NP" & "Disease progression" unrelated to study drug are excluded as AEs.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Pembrolizumab IV + V937 IV
    Reporting group description
    		 -

    Reporting group title
    Pembrolizumab IV
    Reporting group description
    		 -

    Reporting group title
    Pembrolizumab IV + V937 IT
    Reporting group description
    		 -

    Serious adverse events
    		 Pembrolizumab IV + V937 IV Pembrolizumab IV Pembrolizumab IV + V937 IT
    Total subjects affected by serious adverse events
         subjects affected / exposed
    8 / 28 (28.57%)
    4 / 26 (15.38%)
    5 / 28 (17.86%)
         number of deaths (all causes)
    14
    9
    12
         number of deaths resulting from adverse events
    3
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Clear cell renal cell carcinoma
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 26 (3.85%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostatic adenoma
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 26 (3.85%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Axillary pain
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Overlap syndrome
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumonitis
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aspiration
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Psychotic disorder
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 26 (3.85%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 26 (3.85%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 26 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 26 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 26 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 26 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Septic rash
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 26 (3.85%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Type 1 diabetes mellitus
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 26 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Pembrolizumab IV + V937 IV Pembrolizumab IV Pembrolizumab IV + V937 IT
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    27 / 28 (96.43%)
    22 / 26 (84.62%)
    27 / 28 (96.43%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 26 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    3
    0
    3
    Tumour haemorrhage
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 26 (0.00%)
    1 / 28 (3.57%)
         occurrences all number
    2
    0
    1
    Cancer pain
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 26 (0.00%)
    3 / 28 (10.71%)
         occurrences all number
    3
    0
    5
    Basal cell carcinoma
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    8
    0
    0
    Vascular disorders
    Hot flush
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 26 (7.69%)
    0 / 28 (0.00%)
         occurrences all number
    0
    2
    0
    Hypertension
         subjects affected / exposed
    2 / 28 (7.14%)
    5 / 26 (19.23%)
    5 / 28 (17.86%)
         occurrences all number
    2
    6
    7
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 26 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    3
    0
    2
    Asthenia
         subjects affected / exposed
    2 / 28 (7.14%)
    3 / 26 (11.54%)
    3 / 28 (10.71%)
         occurrences all number
    3
    3
    4
    Axillary pain
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 26 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    2
    0
    2
    Fatigue
         subjects affected / exposed
    8 / 28 (28.57%)
    6 / 26 (23.08%)
    11 / 28 (39.29%)
         occurrences all number
    8
    7
    11
    Influenza like illness
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 26 (3.85%)
    2 / 28 (7.14%)
         occurrences all number
    0
    1
    2
    Oedema peripheral
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    3
    0
    0
    Xerosis
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 26 (3.85%)
    2 / 28 (7.14%)
         occurrences all number
    1
    1
    2
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 26 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    2
    0
    2
    Pneumonitis
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    2
    0
    0
    Dyspnoea
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    4 / 28 (14.29%)
         occurrences all number
    1
    0
    4
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    1 / 28 (3.57%)
    2 / 26 (7.69%)
    4 / 28 (14.29%)
         occurrences all number
    1
    2
    4
    Depression
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 26 (7.69%)
    0 / 28 (0.00%)
         occurrences all number
    0
    2
    0
    Anxiety
         subjects affected / exposed
    1 / 28 (3.57%)
    2 / 26 (7.69%)
    0 / 28 (0.00%)
         occurrences all number
    1
    3
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    5 / 28 (17.86%)
    9 / 26 (34.62%)
    5 / 28 (17.86%)
         occurrences all number
    8
    14
    11
    Aspartate aminotransferase increased
         subjects affected / exposed
    5 / 28 (17.86%)
    4 / 26 (15.38%)
    3 / 28 (10.71%)
         occurrences all number
    8
    6
    5
    Blood alkaline phosphatase increased
         subjects affected / exposed
    2 / 28 (7.14%)
    4 / 26 (15.38%)
    3 / 28 (10.71%)
         occurrences all number
    3
    5
    6
    Blood bilirubin increased
         subjects affected / exposed
    1 / 28 (3.57%)
    2 / 26 (7.69%)
    1 / 28 (3.57%)
         occurrences all number
    4
    4
    2
    Blood cholesterol increased
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 26 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    3
    Blood creatinine increased
         subjects affected / exposed
    3 / 28 (10.71%)
    2 / 26 (7.69%)
    1 / 28 (3.57%)
         occurrences all number
    7
    3
    1
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    4 / 28 (14.29%)
    4 / 26 (15.38%)
    2 / 28 (7.14%)
         occurrences all number
    6
    4
    2
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    2 / 28 (7.14%)
    3 / 26 (11.54%)
    3 / 28 (10.71%)
         occurrences all number
    3
    5
    3
    Weight decreased
         subjects affected / exposed
    7 / 28 (25.00%)
    2 / 26 (7.69%)
    3 / 28 (10.71%)
         occurrences all number
    7
    2
    3
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    2
    0
    0
    Fall
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 26 (7.69%)
    0 / 28 (0.00%)
         occurrences all number
    0
    2
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    5 / 28 (17.86%)
    4 / 26 (15.38%)
    1 / 28 (3.57%)
         occurrences all number
    6
    5
    1
    Dizziness
         subjects affected / exposed
    3 / 28 (10.71%)
    4 / 26 (15.38%)
    0 / 28 (0.00%)
         occurrences all number
    3
    4
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    12 / 28 (42.86%)
    7 / 26 (26.92%)
    5 / 28 (17.86%)
         occurrences all number
    15
    8
    9
    Lymphopenia
         subjects affected / exposed
    2 / 28 (7.14%)
    1 / 26 (3.85%)
    1 / 28 (3.57%)
         occurrences all number
    2
    3
    3
    Eosinophilia
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 26 (3.85%)
    3 / 28 (10.71%)
         occurrences all number
    1
    1
    7
    Thrombocytosis
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 26 (0.00%)
    1 / 28 (3.57%)
         occurrences all number
    3
    0
    2
    Neutropenia
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 26 (3.85%)
    2 / 28 (7.14%)
         occurrences all number
    0
    2
    4
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 28 (0.00%)
    4 / 26 (15.38%)
    2 / 28 (7.14%)
         occurrences all number
    0
    4
    2
    Abdominal pain upper
         subjects affected / exposed
    0 / 28 (0.00%)
    3 / 26 (11.54%)
    3 / 28 (10.71%)
         occurrences all number
    0
    4
    3
    Diarrhoea
         subjects affected / exposed
    3 / 28 (10.71%)
    3 / 26 (11.54%)
    4 / 28 (14.29%)
         occurrences all number
    3
    4
    5
    Gastritis
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 26 (0.00%)
    1 / 28 (3.57%)
         occurrences all number
    2
    0
    2
    Nausea
         subjects affected / exposed
    7 / 28 (25.00%)
    2 / 26 (7.69%)
    5 / 28 (17.86%)
         occurrences all number
    10
    3
    6
    Vomiting
         subjects affected / exposed
    4 / 28 (14.29%)
    2 / 26 (7.69%)
    0 / 28 (0.00%)
         occurrences all number
    6
    2
    0
    Constipation
         subjects affected / exposed
    6 / 28 (21.43%)
    5 / 26 (19.23%)
    3 / 28 (10.71%)
         occurrences all number
    8
    5
    3
    Skin and subcutaneous tissue disorders
    Vitiligo
         subjects affected / exposed
    3 / 28 (10.71%)
    3 / 26 (11.54%)
    3 / 28 (10.71%)
         occurrences all number
    3
    3
    3
    Skin lesion
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 26 (0.00%)
    1 / 28 (3.57%)
         occurrences all number
    3
    0
    1
    Rash
         subjects affected / exposed
    4 / 28 (14.29%)
    2 / 26 (7.69%)
    5 / 28 (17.86%)
         occurrences all number
    5
    2
    5
    Pruritus
         subjects affected / exposed
    6 / 28 (21.43%)
    5 / 26 (19.23%)
    6 / 28 (21.43%)
         occurrences all number
    9
    8
    9
    Dermatitis
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 26 (7.69%)
    1 / 28 (3.57%)
         occurrences all number
    0
    2
    1
    Rash maculo-papular
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    1
    0
    2
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    2
    0
    0
    Haematuria
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 26 (7.69%)
    0 / 28 (0.00%)
         occurrences all number
    0
    2
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    3 / 28 (10.71%)
    3 / 26 (11.54%)
    3 / 28 (10.71%)
         occurrences all number
    6
    3
    3
    Hyperthyroidism
         subjects affected / exposed
    3 / 28 (10.71%)
    2 / 26 (7.69%)
    0 / 28 (0.00%)
         occurrences all number
    3
    2
    0
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 26 (3.85%)
    2 / 28 (7.14%)
         occurrences all number
    1
    1
    2
    Arthralgia
         subjects affected / exposed
    4 / 28 (14.29%)
    5 / 26 (19.23%)
    2 / 28 (7.14%)
         occurrences all number
    5
    5
    2
    Back pain
         subjects affected / exposed
    2 / 28 (7.14%)
    2 / 26 (7.69%)
    1 / 28 (3.57%)
         occurrences all number
    2
    3
    1
    Muscle spasms
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 26 (3.85%)
    3 / 28 (10.71%)
         occurrences all number
    1
    1
    4
    Muscular weakness
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 26 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    2
    0
    0
    Myalgia
         subjects affected / exposed
    2 / 28 (7.14%)
    1 / 26 (3.85%)
    1 / 28 (3.57%)
         occurrences all number
    4
    1
    1
    Infections and infestations
    COVID-19
         subjects affected / exposed
    2 / 28 (7.14%)
    2 / 26 (7.69%)
    3 / 28 (10.71%)
         occurrences all number
    2
    2
    5
    Gastroenteritis
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 26 (0.00%)
    3 / 28 (10.71%)
         occurrences all number
    0
    0
    3
    Nasopharyngitis
         subjects affected / exposed
    1 / 28 (3.57%)
    3 / 26 (11.54%)
    1 / 28 (3.57%)
         occurrences all number
    1
    4
    1
    Skin infection
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 26 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    2
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 26 (3.85%)
    4 / 28 (14.29%)
         occurrences all number
    0
    2
    5
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    3 / 28 (10.71%)
    1 / 26 (3.85%)
    3 / 28 (10.71%)
         occurrences all number
    4
    1
    3
    Gout
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 26 (3.85%)
    2 / 28 (7.14%)
         occurrences all number
    0
    2
    3
    Hypercalcaemia
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 26 (3.85%)
    2 / 28 (7.14%)
         occurrences all number
    1
    1
    2
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 26 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    1
    0
    2
    Hyperglycaemia
         subjects affected / exposed
    4 / 28 (14.29%)
    1 / 26 (3.85%)
    2 / 28 (7.14%)
         occurrences all number
    5
    5
    2
    Hyperphosphataemia
         subjects affected / exposed
    3 / 28 (10.71%)
    4 / 26 (15.38%)
    0 / 28 (0.00%)
         occurrences all number
    4
    4
    0
    Hypoalbuminaemia
         subjects affected / exposed
    3 / 28 (10.71%)
    2 / 26 (7.69%)
    2 / 28 (7.14%)
         occurrences all number
    4
    2
    2
    Hypocalcaemia
         subjects affected / exposed
    2 / 28 (7.14%)
    1 / 26 (3.85%)
    0 / 28 (0.00%)
         occurrences all number
    2
    1
    0
    Hypokalaemia
         subjects affected / exposed
    2 / 28 (7.14%)
    2 / 26 (7.69%)
    1 / 28 (3.57%)
         occurrences all number
    3
    4
    1
    Hyponatraemia
         subjects affected / exposed
    3 / 28 (10.71%)
    2 / 26 (7.69%)
    3 / 28 (10.71%)
         occurrences all number
    4
    2
    3

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 May 2020
    The amendment purpose was to change the timing of peripheral blood mononuclear cells (PBMC) collection to Day 1 of Cycle 3, and to indicate it is to be performed only at selected study site(s).
    27 Sep 2020
    The purpose of the amendment was to eliminate the requirement of collecting throat swabs or sputum samples from close contacts or healthcare workers in relation to the viral transmission of V937 from participants. It aimed to address the requests made by the Health Authority and provide further clarifications.
    10 Feb 2021
    This amendment aims to remove C1D1 collection of blood/serum samples from Arm 3 and all biopsies from Arm 3.
    24 Aug 2021
    This amendment is for updating the dose modification and toxicity management guidelines for irAEs.
    30 Aug 2022
    Amendment 5 aimed for Merck Sharp & Dohme Corp. underwent an entity name and address change to Merck Sharp & Dohme LLC, Rahway, NJ, USA. This conversion resulted only in an entity name change and update to the address.
    22 Dec 2022
    Amendment 6 aimed for discontinuation of V937-011 due to the Sponsor’s development decision. The overall rationale for this amendment is to allow eligible participants who are receiving pembrolizumab may be enrolled in a pembrolizumab extension study to continue receiving pembrolizumab monotherapy for up to 35 cycles.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    This study was terminated due to the sponsor’s development decision.
    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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