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    Clinical Trial Results:
    A Phase I/II, Multicenter, Open-label, Clinical Trial of Intratumoral/Intralesional Administration of RGT100 in Subjects with Advanced or Recurrent Tumors

    Summary
    EudraCT number
    2016-003028-22
    Trial protocol
    DE   GB   ES   FR  
    Global end of trial date
    18 May 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    17 May 2019
    First version publication date
    17 May 2019
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    4621-001
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03065023
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Rigontec GMBH Protocol Number: RGT100-001, Merck Protocol Number: MK-4621-001
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., 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
    18 May 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    18 May 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    18 May 2018
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    This is a Phase I/II multicenter, first-in-human open-label, dose escalation study to evaluate the safety, tolerability, and anti-tumor activity of intratumoral (IT)/intralesional (IL) injections of MK-4621 (RGT100) in adult participants with selected advanced or recurrent tumors..
    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
    19 Dec 2016
    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
    Spain: 5
    Country: Number of subjects enrolled
    United Kingdom: 6
    Country: Number of subjects enrolled
    Germany: 4
    Worldwide total number of subjects
    15
    EEA total number of subjects
    15
    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)
    10
    From 65 to 84 years
    5
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Fifteen (15) participants for this study were recruited from four (4) study sites in three (3) countries. Group B was not started.

    Pre-assignment
    Screening details
    Participants with transdermally/transmucosally injectable tumors or injectable liver tumors were screened for this study.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Group A: MK-4621 0.2 mg
    Arm description
    Participants with transdermally/transmucosally injectable tumors including cutaneous, subcutaneous or lymph node injectable tumors received MK-4621 0.2.mg via intratumoral (IT)/intralesional (IL) injection twice each week over a period of 4 weeks during Cycle 1. Participants may have continued to receive study treatment beyond Cycle 1 for the remaining duration of the study as long as clinical benefit (no overt clinical progression or toxicity considered to be intolerable as per Investigator’s assessment) was present (could have been up to approximately 2 years). Each cycle was 28 days.
    Arm type
    Experimental

    Investigational medicinal product name
    MK-4621
    Investigational medicinal product code
    Other name
    RGT100
    Pharmaceutical forms
    Dispersion for injection
    Routes of administration
    Intratumoral use, Intralesional use
    Dosage and administration details
    MK-4621 0.2 mg via intratumoral (IT) or intralesional (IL) injection

    Arm title
    Group A: MK-4621 0.4 mg
    Arm description
    Participants with transdermally/transmucosally injectable tumors including cutaneous, subcutaneous or lymph node injectable tumors received MK-4621 0.4 mg via IT/IL injection twice each week over a period of 4 weeks during Cycle 1. Participants may have continued to receive study treatment beyond Cycle 1 for the remaining duration of the study as long as clinical benefit (no overt clinical progression or toxicity considered to be intolerable as per Investigator’s assessment) was present (could have been up to approximately 2 years). Each cycle was 28 days.
    Arm type
    Experimental

    Investigational medicinal product name
    MK-4621
    Investigational medicinal product code
    Other name
    RGT100
    Pharmaceutical forms
    Dispersion for injection
    Routes of administration
    Intratumoral use, Intralesional use
    Dosage and administration details
    MK-4621 0.4 mg via intratumoral (IT) or intralesional (IL) injection

    Arm title
    Group A: MK-4621 0.6 mg
    Arm description
    Participants with transdermally/transmucosally injectable tumors including cutaneous, subcutaneous or lymph node injectable tumors received MK-4621 0.6 mg via IT/IL injection twice each week over a period of 4 weeks during Cycle 1. Participants may have continued to receive study treatment beyond Cycle 1 for the remaining duration of the study as long as clinical benefit (no overt clinical progression or toxicity considered to be intolerable as per Investigator’s assessment) was present (could have been up to approximately 2 years). Each cycle was 28 days.
    Arm type
    Experimental

    Investigational medicinal product name
    MK-4621
    Investigational medicinal product code
    Other name
    RGT100
    Pharmaceutical forms
    Dispersion for injection
    Routes of administration
    Intratumoral use, Intralesional use
    Dosage and administration details
    MK-4621 0.6 mg via intratumoral (IT) or intralesional (IL) injection

    Arm title
    Group A: MK-4621 0.8 mg
    Arm description
    Participants with transdermally/transmucosally injectable tumors including cutaneous, subcutaneous or lymph node injectable tumors received MK-4621 0.8 mg via IT/IL injection twice each week over a period of 4 weeks during Cycle 1. Participants may have continued to receive study treatment beyond Cycle 1 for the remaining duration of the study as long as clinical benefit (no overt clinical progression or toxicity considered to be intolerable as per Investigator’s assessment) was present (could have been up to approximately 2 years). Each cycle was 28 days.
    Arm type
    Experimental

    Investigational medicinal product name
    MK-4621
    Investigational medicinal product code
    Other name
    RGT100
    Pharmaceutical forms
    Dispersion for injection
    Routes of administration
    Intratumoral use, Intralesional use
    Dosage and administration details
    MK-4621 0.8 mg via intratumoral (IT) or intralesional (IL) injection

    Number of subjects in period 1
    Group A: MK-4621 0.2 mg Group A: MK-4621 0.4 mg Group A: MK-4621 0.6 mg Group A: MK-4621 0.8 mg
    Started
    3
    3
    3
    6
    Completed
    1
    1
    2
    3
    Not completed
    2
    2
    1
    3
         Participant Decision
    -
    -
    -
    1
         Adverse event, serious fatal
    2
    -
    1
    1
         Progressive Disease
    -
    1
    -
    -
         Consent withdrawn by subject
    -
    -
    -
    1
         Lost to follow-up
    -
    1
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Group A: MK-4621 0.2 mg
    Reporting group description
    Participants with transdermally/transmucosally injectable tumors including cutaneous, subcutaneous or lymph node injectable tumors received MK-4621 0.2.mg via intratumoral (IT)/intralesional (IL) injection twice each week over a period of 4 weeks during Cycle 1. Participants may have continued to receive study treatment beyond Cycle 1 for the remaining duration of the study as long as clinical benefit (no overt clinical progression or toxicity considered to be intolerable as per Investigator’s assessment) was present (could have been up to approximately 2 years). Each cycle was 28 days.

    Reporting group title
    Group A: MK-4621 0.4 mg
    Reporting group description
    Participants with transdermally/transmucosally injectable tumors including cutaneous, subcutaneous or lymph node injectable tumors received MK-4621 0.4 mg via IT/IL injection twice each week over a period of 4 weeks during Cycle 1. Participants may have continued to receive study treatment beyond Cycle 1 for the remaining duration of the study as long as clinical benefit (no overt clinical progression or toxicity considered to be intolerable as per Investigator’s assessment) was present (could have been up to approximately 2 years). Each cycle was 28 days.

    Reporting group title
    Group A: MK-4621 0.6 mg
    Reporting group description
    Participants with transdermally/transmucosally injectable tumors including cutaneous, subcutaneous or lymph node injectable tumors received MK-4621 0.6 mg via IT/IL injection twice each week over a period of 4 weeks during Cycle 1. Participants may have continued to receive study treatment beyond Cycle 1 for the remaining duration of the study as long as clinical benefit (no overt clinical progression or toxicity considered to be intolerable as per Investigator’s assessment) was present (could have been up to approximately 2 years). Each cycle was 28 days.

    Reporting group title
    Group A: MK-4621 0.8 mg
    Reporting group description
    Participants with transdermally/transmucosally injectable tumors including cutaneous, subcutaneous or lymph node injectable tumors received MK-4621 0.8 mg via IT/IL injection twice each week over a period of 4 weeks during Cycle 1. Participants may have continued to receive study treatment beyond Cycle 1 for the remaining duration of the study as long as clinical benefit (no overt clinical progression or toxicity considered to be intolerable as per Investigator’s assessment) was present (could have been up to approximately 2 years). Each cycle was 28 days.

    Reporting group values
    Group A: MK-4621 0.2 mg Group A: MK-4621 0.4 mg Group A: MK-4621 0.6 mg Group A: MK-4621 0.8 mg Total
    Number of subjects
    3 3 3 6 15
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    2 2 2 4 10
        From 65-84 years
    1 1 1 2 5
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    51.7 ± 26.8 48.7 ± 18.1 55.3 ± 16.0 64.2 ± 8.3 -
    Sex: Female, Male
    Units: Subjects
        Female
    2 1 2 2 7
        Male
    1 2 1 4 8
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 0 0 0 0
        Asian
    0 0 0 0 0
        Native Hawaiian or Other Pacific Islander
    0 0 0 0 0
        Black or African American
    0 0 0 0 0
        White
    3 3 3 6 15
        More than one race
    0 0 0 0 0
        Unknown or Not Reported
    0 0 0 0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    0 0 0 0 0
        Not Hispanic or Latino
    3 3 3 6 15
        Unknown or Not Reported
    0 0 0 0 0
    Plasma Cytokine Release: Interleukin-6
    Blood samples were collected at baseline for the analysis of cytokine release for Interleukin-6 (IL-6) in plasma.
    Units: ng/L
        median (full range (min-max))
    9.3 (9.3 to 9.3) 9.3 (9.3 to 31.5) 10 (7.5 to 12.9) 7.5 (7.5 to 15.6) -
    Plasma Cytokine Release: Tumor Necrosis Factor-alpha (TNF-a)
    Blood samples were collected at baseline for the analysis of cytokine release for tumor necrosis factor-alpha [TNF-a]) in plasma.
    Units: ng/L
        median (full range (min-max))
    8.3 (8.3 to 8.3) 8.3 (8.3 to 8.3) 24.2 (9.7 to 24.4) 9.7 (9.7 to 30.4) -

    End points

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    End points reporting groups
    Reporting group title
    Group A: MK-4621 0.2 mg
    Reporting group description
    Participants with transdermally/transmucosally injectable tumors including cutaneous, subcutaneous or lymph node injectable tumors received MK-4621 0.2.mg via intratumoral (IT)/intralesional (IL) injection twice each week over a period of 4 weeks during Cycle 1. Participants may have continued to receive study treatment beyond Cycle 1 for the remaining duration of the study as long as clinical benefit (no overt clinical progression or toxicity considered to be intolerable as per Investigator’s assessment) was present (could have been up to approximately 2 years). Each cycle was 28 days.

    Reporting group title
    Group A: MK-4621 0.4 mg
    Reporting group description
    Participants with transdermally/transmucosally injectable tumors including cutaneous, subcutaneous or lymph node injectable tumors received MK-4621 0.4 mg via IT/IL injection twice each week over a period of 4 weeks during Cycle 1. Participants may have continued to receive study treatment beyond Cycle 1 for the remaining duration of the study as long as clinical benefit (no overt clinical progression or toxicity considered to be intolerable as per Investigator’s assessment) was present (could have been up to approximately 2 years). Each cycle was 28 days.

    Reporting group title
    Group A: MK-4621 0.6 mg
    Reporting group description
    Participants with transdermally/transmucosally injectable tumors including cutaneous, subcutaneous or lymph node injectable tumors received MK-4621 0.6 mg via IT/IL injection twice each week over a period of 4 weeks during Cycle 1. Participants may have continued to receive study treatment beyond Cycle 1 for the remaining duration of the study as long as clinical benefit (no overt clinical progression or toxicity considered to be intolerable as per Investigator’s assessment) was present (could have been up to approximately 2 years). Each cycle was 28 days.

    Reporting group title
    Group A: MK-4621 0.8 mg
    Reporting group description
    Participants with transdermally/transmucosally injectable tumors including cutaneous, subcutaneous or lymph node injectable tumors received MK-4621 0.8 mg via IT/IL injection twice each week over a period of 4 weeks during Cycle 1. Participants may have continued to receive study treatment beyond Cycle 1 for the remaining duration of the study as long as clinical benefit (no overt clinical progression or toxicity considered to be intolerable as per Investigator’s assessment) was present (could have been up to approximately 2 years). Each cycle was 28 days.

    Primary: Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria

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    End point title
    Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria [1]
    End point description
    An AE was defined as any untoward medical occurrence in a study participant administered study treatment which did not necessarily have a causal relationship with this treatment. Treatment-related was defined as having a “Possible” or “Related” relationship to study treatment, as assessed by the Investigator. Severity of AE referred to the extent to which an AE affected the participants daily activities as assessed by the Investigator and was based on NCI CTCAE grades: Grade 1 (Mild); Grade 2 (Moderate); Grade 3 (Severe or medically significant but not immediately life-threatening); Grade 4 (Life-threatening consequences); or Grade 5 (Death related to AE). The number of participants who experienced at least one treatment-related AE or laboratory abnormality are presented by severity. The safety population consisted of all participants who received ≥1 injection of MK-4621.
    End point type
    Primary
    End point timeframe
    Up to 90 days post last injection (Up to approximately 192 days)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for or conducted for this end point.
    End point values
    Group A: MK-4621 0.2 mg Group A: MK-4621 0.4 mg Group A: MK-4621 0.6 mg Group A: MK-4621 0.8 mg
    Number of subjects analysed
    3
    3
    3
    6
    Units: Participants
        Grade 1
    1
    2
    2
    3
        Grade 2
    0
    1
    1
    2
        Grade 3
    1
    0
    0
    1
        Grade 4
    0
    0
    0
    0
        Grade 5
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Number of Participants Who Experienced a Serious Adverse Event (SAE)

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    End point title
    Number of Participants Who Experienced a Serious Adverse Event (SAE) [2]
    End point description
    A SAE was defined as any AE, regardless of dose, causality or expectedness, that: • Resulted in death; • Was life-threatening; • Required inpatient hospitalization or prolonged existing inpatient hospitalization; • Resulted in persistent or significant incapacity or disability; • Was a congenital anomaly or birth defect; or • Was any other medically important event. The safety population consisted of all participants who received ≥1 injection of MK-4621.
    End point type
    Primary
    End point timeframe
    Up to 90 days post last injection (Up to approximately 192 days)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for or conducted for this end point.
    End point values
    Group A: MK-4621 0.2 mg Group A: MK-4621 0.4 mg Group A: MK-4621 0.6 mg Group A: MK-4621 0.8 mg
    Number of subjects analysed
    3
    3
    3
    6
    Units: Participants
    2
    2
    1
    3
    No statistical analyses for this end point

    Primary: Number of Participants Who Discontinued Study Treatment Due to a Treatment-related Adverse Event (AE)

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    End point title
    Number of Participants Who Discontinued Study Treatment Due to a Treatment-related Adverse Event (AE) [3]
    End point description
    An AE was defined as any untoward medical occurrence in a study participant administered a study treatment which did not necessarily have a causal relationship with this treatment. Treatment-related was defined as having a “Possible” or “Related” relationship to study treatment, as assessed by the Investigator. The number of participants who discontinued study treatment due to a treatment-related AE is presented. The safety population consisted of all participants who received ≥1 injection of MK-4621.
    End point type
    Primary
    End point timeframe
    Up to last injection (Up to approximately 102 days)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for or conducted for this end point.
    End point values
    Group A: MK-4621 0.2 mg Group A: MK-4621 0.4 mg Group A: MK-4621 0.6 mg Group A: MK-4621 0.8 mg
    Number of subjects analysed
    3
    3
    3
    6
    Units: Participants
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria

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    End point title
    Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria [4]
    End point description
    DLTs were assessed during the 1st treatment cycle (28 days) & were defined as any drug-related toxicity that occurred during the 28-day DLT period & included: • Non-hematologic toxicity Grade ≥3 (except diarrhea, nausea, & vomiting unless lasting >3 days despite optimal supportive care); • Confirmed non-hematologic appropriately graded laboratory findings of Grade ≥3 that were ≤ Grade 1 at baseline; • Hematologic toxicity: Grade 4 neutropenia ≥5 days, or Grade 3 neutropenia with fever (fever is >38.4ºC); Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia lasting >7 days or with bleeding; and • Any other toxicity assessed as related to MK-4621, & which, in the opinion of the Investigator & the Sponsor physician constituted a DLT. The number of participants who experienced a DLT is presented by NCI CTCAE version 4.03 severity grade. The DLT evaluable population consisted of participants who completed Cycle 1 (Day 28) or withdrew early for experiencing a DLT.
    End point type
    Primary
    End point timeframe
    Cycle 1 (Up to approximately 28 days); Each cycle was 28 days.
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for or conducted for this end point.
    End point values
    Group A: MK-4621 0.2 mg Group A: MK-4621 0.4 mg Group A: MK-4621 0.6 mg Group A: MK-4621 0.8 mg
    Number of subjects analysed
    3
    3
    3
    6
    Units: Participants
        Grade 1
    0
    0
    0
    0
        Grade 2
    0
    0
    0
    0
        Grade 3
    0
    0
    0
    0
        Grade 4
    0
    0
    0
    0
        Grade 5
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Objective Response Rate as Evaluated Radiologically Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)

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    End point title
    Objective Response Rate as Evaluated Radiologically Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
    End point description
    ORR was defined as the percentage of participants who had a Complete Response (CR) or a Partial Response. Per irRECIST, CR (irCR) was defined as the complete disappearance of all measurable and non-measurable lesions. Lymph nodes must also have decreased to <0 mm in short axis. And, per irRECIST, Partial Response (irPR) was defined as a decrease of ≥30% in total measured tumor burden (TMTB) relative to baseline. For this study, irRECIST was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced an irCR or irPR based on irRECIST is presented. The efficacy population consisted of all allocated participants.
    End point type
    Secondary
    End point timeframe
    Up to 60 days post last injection (Up to approximately 162 days)
    End point values
    Group A: MK-4621 0.2 mg Group A: MK-4621 0.4 mg Group A: MK-4621 0.6 mg Group A: MK-4621 0.8 mg
    Number of subjects analysed
    3
    3
    3
    6
    Units: Percentage of Participants
        number (confidence interval 95%)
    0 (0.0 to 70.8)
    0 (0.0 to 70.8)
    0 (0.0 to 70.8)
    0 (0.0 to 45.9)
    No statistical analyses for this end point

    Other pre-specified: Mean Fold Change from Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (6 Hours Post Injection)

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    End point title
    Mean Fold Change from Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (6 Hours Post Injection)
    End point description
    Blood samples were collected at various time points for the analysis of mean fold change from baseline in cytokine release for selected cytokines (Interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-a]) in plasma. The cytokine evaluable population consisted of all participants who received ≥1 injection of MK-4621 and had baseline and post treatment cytokine data for this end point.
    End point type
    Other pre-specified
    End point timeframe
    Baseline and Cycle 1 Day 1 (6 hours post injection) (Up to 1 day); Each cycle was 28 days.
    End point values
    Group A: MK-4621 0.2 mg Group A: MK-4621 0.4 mg Group A: MK-4621 0.6 mg Group A: MK-4621 0.8 mg
    Number of subjects analysed
    3
    3
    3
    6
    Units: Fold change
    arithmetic mean (standard deviation)
        IL-6
    1 ± 0
    1.95 ± 1.64
    2.71 ± 2.34
    2.52 ± 3.14
        TNF-a
    1 ± 0
    1 ± 0
    1 ± 0.6
    0.89 ± 0.28
    No statistical analyses for this end point

    Other pre-specified: Mean Fold Change from Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (24 Hours Post Injection)

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    End point title
    Mean Fold Change from Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (24 Hours Post Injection)
    End point description
    Blood samples were collected at various time points for the analysis of mean fold change from baseline in cytokine release for selected cytokines (Interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-a]) in plasma. The cytokine evaluable population consisted of all participants who received ≥1 injection of MK-4621 and had baseline and post treatment cytokine data for this end point.
    End point type
    Other pre-specified
    End point timeframe
    Baseline and Cycle 1 Day 1 (24 hours post injection) (Up to 2 days); Each cycle was 28 days.
    End point values
    Group A: MK-4621 0.2 mg Group A: MK-4621 0.4 mg Group A: MK-4621 0.6 mg Group A: MK-4621 0.8 mg
    Number of subjects analysed
    2
    3
    3
    6
    Units: Fold change
    arithmetic mean (standard deviation)
        IL-6
    1 ± 0
    1.27 ± 0.46
    1.14 ± 0.3
    1.68 ± 0.97
        TNF-a
    1 ± 0
    1 ± 0
    1.48 ± 1.44
    0.89 ± 0.28
    No statistical analyses for this end point

    Other pre-specified: Mean Fold Change from Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (6 Hours Post Injection)

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    End point title
    Mean Fold Change from Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (6 Hours Post Injection)
    End point description
    Blood samples were collected at various time points for the analysis of mean fold change from baseline in cytokine release for selected cytokines (Interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-a]) in plasma. The cytokine evaluable population consisted of all participants who received ≥1 injection of MK-4621 and had baseline and post treatment cytokine data for this end point.
    End point type
    Other pre-specified
    End point timeframe
    Baseline and Cycle 1 Day 25 (6 hours post injection) (Up to 25 days); Each cycle was 28 days.
    End point values
    Group A: MK-4621 0.2 mg Group A: MK-4621 0.4 mg Group A: MK-4621 0.6 mg Group A: MK-4621 0.8 mg
    Number of subjects analysed
    3
    3
    3
    5
    Units: Fold change
    arithmetic mean (standard deviation)
        IL-6
    0.95 ± 0.08
    2 ± 1.11
    1.02 ± 0.31
    1.5 ± 0.61
        TNF-a
    1 ± 0
    1 ± 0
    0.77 ± 0.21
    0.77 ± 0.29
    No statistical analyses for this end point

    Other pre-specified: Mean Fold Change from Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (24 Hours Post Injection)

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    End point title
    Mean Fold Change from Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (24 Hours Post Injection)
    End point description
    Blood samples were collected at various time points for the analysis of mean fold change from baseline in cytokine release for selected cytokines (Interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-a]) in plasma. The cytokine evaluable population consisted of all participants who received ≥1 injection of MK-4621 and had baseline and post treatment cytokine data for this end point.
    End point type
    Other pre-specified
    End point timeframe
    Baseline and Cycle 1 Day 25 (24 hours post injection) (Up to 26 days); Each cycle was 28 days.
    End point values
    Group A: MK-4621 0.2 mg Group A: MK-4621 0.4 mg Group A: MK-4621 0.6 mg Group A: MK-4621 0.8 mg
    Number of subjects analysed
    3
    3
    3
    5
    Units: Fold change
    arithmetic mean (standard deviation)
        IL-6
    1.52 ± 0.9
    1 ± 0
    0.99 ± 0.1
    0.89 ± 0.19
        TNF-a
    1 ± 0
    1 ± 0
    1.02 ± 0.63
    0.88 ± 0.32
    No statistical analyses for this end point

    Other pre-specified: Area Under the Concentration-Time Curve From Start of Dosing to Last Observed Concentration Above Limit of Quantitation (AUC0-t) of MK-4621: Day 1

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    End point title
    Area Under the Concentration-Time Curve From Start of Dosing to Last Observed Concentration Above Limit of Quantitation (AUC0-t) of MK-4621: Day 1
    End point description
    Blood samples were collected at various time points during Cycle 1 for the determination of MK-4621 AUC0-t on Day 1, which was defined as the AUC from the start time of dosing to the time of the last observed concentration above the limit of quantitation (LOQ). The pharmacokinetic (PK) evaluable population consisted of all participants who received ≥1 injection of MK-4621 and had pre- and post-treatment PK data for this end point.
    End point type
    Other pre-specified
    End point timeframe
    Cycle 1 Day 1: Predose, 5 and 30 minutes, 2, 4, 6 and 24 hours post dose (Up to 2 days); Each cycle was 28 days.
    End point values
    Group A: MK-4621 0.2 mg Group A: MK-4621 0.4 mg Group A: MK-4621 0.6 mg Group A: MK-4621 0.8 mg
    Number of subjects analysed
    3
    3
    3
    6
    Units: h*ng/mL
        arithmetic mean (standard deviation)
    0.00 ± 0.00
    0.174 ± 0.157
    0.0360 ± 0.0623
    1.87 ± 4.55
    No statistical analyses for this end point

    Other pre-specified: Area Under the Concentration-Time Curve From Start of Dosing to Last Observed Concentration Above Limit of Quantitation (AUC0-t) of MK-4621: Day 25

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    End point title
    Area Under the Concentration-Time Curve From Start of Dosing to Last Observed Concentration Above Limit of Quantitation (AUC0-t) of MK-4621: Day 25
    End point description
    Blood samples were collected at various time points during Cycle 1 for the determination of MK-4621 AUC0-t on Day 25, which was defined as the AUC from the start time of dosing to the time of the last observed concentration above the limit of quantitation (LOQ). The PK evaluable population consisted of all participants who received ≥1 injection of MK-4621 and had pre- and post-treatment PK data for this end point.
    End point type
    Other pre-specified
    End point timeframe
    Cycle 1 Day 25: Predose, 5 and 30 minutes, 2, 4, 6 and 24 hours post dose (Up to 26 days); Each cycle was 28 days.
    End point values
    Group A: MK-4621 0.2 mg Group A: MK-4621 0.4 mg Group A: MK-4621 0.6 mg Group A: MK-4621 0.8 mg
    Number of subjects analysed
    3
    3
    3
    5
    Units: h*ng/mL
        arithmetic mean (standard deviation)
    0.00 ± 0.00
    1.07 ± 0.767
    0.099 ± 0.172
    0.156 ± 0.350
    No statistical analyses for this end point

    Other pre-specified: Maximum Plasma Concentration (Cmax) of MK-4621: Day 1

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    End point title
    Maximum Plasma Concentration (Cmax) of MK-4621: Day 1
    End point description
    Blood samples were collected at various time points during Cycle 1 for the determination of MK-4621 Cmax on Day 1. The PK evaluable population consisted of all participants who received ≥1 injection of MK-4621 and had pre- and post-treatment PK data for this end point.
    End point type
    Other pre-specified
    End point timeframe
    Cycle 1 Day 1: Predose, 5 and 30 minutes, 2, 4, 6 and 24 hours post dose (Up to 2 days); Each cycle was 28 days.
    End point values
    Group A: MK-4621 0.2 mg Group A: MK-4621 0.4 mg Group A: MK-4621 0.6 mg Group A: MK-4621 0.8 mg
    Number of subjects analysed
    3
    3
    3
    6
    Units: ng/mL
        arithmetic mean (standard deviation)
    0.00 ± 0.00
    4.18 ± 3.76
    0.863 ± 1.50
    9.24 ± 21.9
    No statistical analyses for this end point

    Other pre-specified: Maximum Plasma Concentration (Cmax) of MK-4621: Day 25

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    End point title
    Maximum Plasma Concentration (Cmax) of MK-4621: Day 25
    End point description
    Blood samples were collected at various time points during Cycle 1 for the determination of MK-4621 Cmax on Day 25. The PK evaluable population consisted of all participants who received ≥1 injection of MK-4621 and had pre- and post-treatment PK data for this end point.
    End point type
    Other pre-specified
    End point timeframe
    Cycle 1 Day 25: Predose, 5 and 30 minutes, 2, 4, 6 and 24 hours post dose (Up to 26 days); Each cycle was 28 days.
    End point values
    Group A: MK-4621 0.2 mg Group A: MK-4621 0.4 mg Group A: MK-4621 0.6 mg Group A: MK-4621 0.8 mg
    Number of subjects analysed
    3
    3
    3
    5
    Units: ng/mL
        arithmetic mean (standard deviation)
    0.00 ± 0.00
    7.43 ± 2.44
    1.703 ± 2.95
    3.75 ± 8.39
    No statistical analyses for this end point

    Other pre-specified: Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 1

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    End point title
    Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 1
    End point description
    Sequential participant tumor biopsies were assessed via immunohistochemistry for the presence of tumor infiltrating CD3 T cell co-receptor-marked cells and Ki-67 nuclear protein-marked cells in tumor biopsies. CD3 is a marker of T cells and Ki-67 is a cell marker of proliferation and activation. The percentage of positive CD3-marked cells and double-positive CD3 and Ki-67 nuclear protein-marked cells in tumor biopsies predose on Day 1 are presented. The immune infiltration evaluable population consisted of all participants who received ≥1 injection of MK-4621 and had pre- and post-treatment immune infiltration data for this end point.
    End point type
    Other pre-specified
    End point timeframe
    Day 1 prior to injection (Up to 1 day)
    End point values
    Group A: MK-4621 0.2 mg Group A: MK-4621 0.4 mg Group A: MK-4621 0.6 mg Group A: MK-4621 0.8 mg
    Number of subjects analysed
    1
    3
    1
    1
    Units: Percentage Positive Cells
    median (full range (min-max))
        CD3 Cells
    8.81 (8.81 to 8.81)
    17.58 (7.03 to 20.81)
    34.64 (34.64 to 34.64)
    17.34 (17.34 to 17.34)
        Ki-67 Positive CD3 Cells
    25.44 (25.44 to 25.44)
    25.19 (18.46 to 48.86)
    39.23 (39.23 to 39.23)
    32.19 (32.19 to 32.19)
    No statistical analyses for this end point

    Other pre-specified: Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 25

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    End point title
    Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 25
    End point description
    Sequential participant tumor biopsies were assessed via immunohistochemistry for the presence of tumor infiltrating CD3 T cell co-receptor-marked cells and Ki-67 nuclear protein-marked cells in tumor biopsies. CD3 is a marker of T cells and Ki-67 is a cell marker of proliferation and activation. The percentage of positive CD3-marked cells and double-positive CD3 and Ki-67 nuclear protein-marked cells in tumor biopsies postdose on Day 25 are presented. The immune infiltration evaluable population consisted of all participants who received ≥1 injection of MK-4621 and had pre- and post-treatment immune infiltration data for this end point.
    End point type
    Other pre-specified
    End point timeframe
    Day 25 post injection (Up to 25 days)
    End point values
    Group A: MK-4621 0.2 mg Group A: MK-4621 0.4 mg Group A: MK-4621 0.6 mg Group A: MK-4621 0.8 mg
    Number of subjects analysed
    1
    3
    1
    1
    Units: Percentage Positive Cells
    median (full range (min-max))
        CD3 Cells
    12.72 (12.72 to 12.72)
    8.43 (8.09 to 12.00)
    11.77 (11.77 to 11.77)
    32.19 (32.19 to 32.19)
        Ki-67 Positive CD3 Cells
    16.96 (16.96 to 16.96)
    36.39 (35.81 to 48.32)
    17.93 (17.93 to 17.93)
    12.16 (12.16 to 12.16)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose through up to 90 days after last dose (Up to approximately 192 days)
    Adverse event reporting additional description
    All participants who received ≥1 injection of MK-4621. Per protocol, disease progression of study cancer was not considered an AE unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" & "Disease progression" not related to study treatment are excluded as AEs.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    Group A: MK-4621 0.2 mg
    Reporting group description
    -

    Reporting group title
    Group A: MK-4621 0.4 mg
    Reporting group description
    -

    Reporting group title
    Group A: MK-4621 0.6 mg
    Reporting group description
    -

    Reporting group title
    Group A: MK-4621 0.8 mg
    Reporting group description
    -

    Serious adverse events
    Group A: MK-4621 0.2 mg Group A: MK-4621 0.4 mg Group A: MK-4621 0.6 mg Group A: MK-4621 0.8 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 3 (66.67%)
    2 / 3 (66.67%)
    1 / 3 (33.33%)
    3 / 6 (50.00%)
         number of deaths (all causes)
    2
    0
    1
    1
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Vascular disorders
    Haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasm progression
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Disease progression
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Pyrexia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Breast swelling
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Device related infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Group A: MK-4621 0.2 mg Group A: MK-4621 0.4 mg Group A: MK-4621 0.6 mg Group A: MK-4621 0.8 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    6 / 6 (100.00%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    1
    General disorders and administration site conditions
    Axillary pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Chills
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    3 / 6 (50.00%)
         occurrences all number
    0
    1
    0
    3
    Chest pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Fatigue
         subjects affected / exposed
    3 / 3 (100.00%)
    0 / 3 (0.00%)
    2 / 3 (66.67%)
    5 / 6 (83.33%)
         occurrences all number
    3
    0
    2
    6
    Induration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Inflammation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Injection site erythema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Injection site bruising
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Injection site haematoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Injection site inflammation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Injection site pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Injection site reaction
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Localised oedema
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Pyrexia
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    5 / 6 (83.33%)
         occurrences all number
    0
    4
    4
    8
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    0
    2
    Injury, poisoning and procedural complications
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Wound
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Investigations
    Body temperature increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Procalcitonin increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Cardiac disorders
    Sinus tachycardia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Tachycardia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    0
    1
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Lymphadenopathy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Dyspnoea
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    0
    1
    Pneumothorax
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Nasal discomfort
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Productive cough
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Sinus disorder
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Nervous system disorders
    Cognitive disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    3
    Headache
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    2 / 3 (66.67%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    2
    1
    Dysgeusia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Presyncope
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    2
    Eye disorders
    Blindness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Gastrointestinal disorders
    Anal haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Diarrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    2
    Constipation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Mouth ulceration
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Nausea
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    2 / 3 (66.67%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    2
    2
    Stomatitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Toothache
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Vomiting
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    1
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Night sweats
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Skin mass
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Muscle contracture
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Myalgia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    1
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Hypophosphataemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Iron deficiency
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Apr 2017
    Amendment 2.0: The purpose of this amendment was to provide clarifying information on the following topics: • Decision making between dose levels in dose escalation and initiation of dose expansion; • Dose volume intratumoral administration and lesion size; • Participant enrollment and slot allocation procedures; • Safety measures and observation period of participants; and • Role of Safety Review Committee (SRC).

    Interruptions (globally)

    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    18 May 2018
    Group B not started for business reasons.
    -

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Group B not started for business reasons.
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