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A Study of Intratumoral/Intralesional Administration of V938 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic or Recurrent Malignancies (V938-001)

NCT04135352

Description:

The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics, and V938 shedding in participants with advanced/metastatic or recurrent malignancies who receive V938 in Combination with Pembrolizumab (MK-3475). The primary objective is to determine the safety and tolerability and to establish a preliminary recommended Phase 2 dose (PRP2D) of V938 administered in combination with pembrolizumab.

Related Conditions:
  • Cutaneous Melanoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Intratumoral/Intralesional Administration of V938 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic or Recurrent Malignancies (V938-001)
  • Official Title: A Phase 1/1b, Open-label Clinical Study of Intratumoral/Intralesional Administration of V938 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic or Recurrent Malignancies

Clinical Trial IDs

  • ORG STUDY ID: V938-001
  • SECONDARY ID: V938-001
  • NCT ID: NCT04135352

Conditions

  • Neoplasm Metastasis

Interventions

DrugSynonymsArms
200 mg of pembrolizumabMK-3475Arm A: Dose Confirmation, Melanoma
V938Arm A: Dose Confirmation, Melanoma

Purpose

The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics, and V938 shedding in participants with advanced/metastatic or recurrent malignancies who receive V938 in Combination with Pembrolizumab (MK-3475). The primary objective is to determine the safety and tolerability and to establish a preliminary recommended Phase 2 dose (PRP2D) of V938 administered in combination with pembrolizumab.

Trial Arms

NameTypeDescriptionInterventions
V938 Dose A + 200 mg of pembrolizumabExperimentalThis arm will enroll participants with advanced/metastatic or recurrent solid tumors. Participants receive Dose A of V938 intratumorally in cycle 1. Participants also receive 200 mg of pembrolizumab intravenously on day 1 of every cycle beginning with cycle 2 for a maximum of 35 cycles. Each cycle is 21 days.
  • 200 mg of pembrolizumab
  • V938
V938 Dose B + 200 mg of pembrolizumabExperimentalThis arm will enroll participants with advanced/metastatic or recurrent solid tumors. Participants receive Dose B of V938 intratumorally in cycle 1. Participants also receive 200 mg of pembrolizumab intravenously on day 1 of every cycle beginning with cycle 2 for a maximum of 35 cycles. Each cycle is 21 days.
  • 200 mg of pembrolizumab
  • V938
V938 Dose C + 200 mg of pembrolizumabExperimentalThis arm will enroll participants with advanced/metastatic or recurrent solid tumors. Participants receive Dose C of V938 intratumorally in cycle 1. Participants also receive 200 mg of pembrolizumab intravenously on day 1 of every cycle beginning with cycle 2 for a maximum of 35 cycles. Each cycle is 21 days.
  • 200 mg of pembrolizumab
  • V938
Arm A: Dose Confirmation, MelanomaExperimentalThis arm will enroll only participants with with a diagnosis of stage III (unresectable) and Stage IV melanoma (any line of therapy). Participants receive V938 at the preliminary recommended Phase 2 Dose, determined by analysis of the Dose A-C arms, intratumorally in cycle 1. Participants also receive 200 mg of pembrolizumab intravenously on day 1 of every cycle beginning with cycle 2 for a maximum of 35 cycles. Each cycle is 21 days.
  • 200 mg of pembrolizumab
  • V938
Arm B: Dose Confirmation, HNSCCExperimentalThis arm will only enroll participants with a diagnosis of advanced/metastatic head and neck squamous cell carcinoma (HNSCC). Participants receive V938 at the preliminary recommended Phase 2 Dose, determined by analysis of the Dose A-C arms, intratumorally in cycle 1. Participants also receive 200 mg of pembrolizumab intravenously on day 1 of every cycle beginning with cycle 2 for a maximum of 35 cycles. Each cycle is 21 days.
  • 200 mg of pembrolizumab
  • V938

Eligibility Criteria

        Inclusion Criteria:

          -  For Dose-escalation Phase (Doses A-C): Have a histologically or cytologically
             confirmed advanced/metastatic solid tumor by pathology report and have received, been
             intolerant to, or been ineligible for treatments known to confer clinical benefit.

          -  For Dose Confirmation Arm A: Have a histologically or cytologically confirmed Stage
             III (unresectable) or Stage IV cutaneous melanoma and have received, been intolerant
             to, or been ineligible for treatments known to confer clinical benefit.

          -  For Dose Confirmation Arm B: Have a histologically or cytologically confirmed advanced
             head and neck squamous cell carcinoma (HNSCC) and have received, been intolerant to,
             or been ineligible for treatment known to confer clinical benefit.

          -  For Dose Confirmation Arms A and B: Have at least 1 lesion that is amenable to both
             intratumoral injection and biopsy.

          -  For all arms: Have at least 1 cutaneous or subcutaneous lesion amenable to
             intratumoral injection, and have at least 1 distant and/or discrete noninjected lesion
             that is measurable per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
             criteria.

          -  For all arms, the injectable lesion must be measurable and meet protocol-specified
             size criteria.

          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale.

          -  Demonstrate adequate organ function.

          -  Male participants are eligible to participate if they agree to the following during
             the intervention period and for at least 120 days: Refrain from donating sperm; PLUS
             either be abstinent from heterosexual intercourse as their preferred and usual
             lifestyle and agree to remain abstinent, OR must agree to use contraception unless
             confirmed to be azoospermic.

          -  Female participant is eligible to participate if she is not pregnant or breastfeeding,
             and at least one of the following conditions applies:

               -  Is not a woman of childbearing potential (WOCBP)

               -  Is a WOCBP and using a contraceptive method that is highly effective, or be
                  abstinent from heterosexual intercourse as their preferred and usual lifestyle
                  (abstinent on a long term and persistent basis), during the intervention period
                  and for at least 120 days after the last dose of study intervention.

          -  HIV-infected participants must have well controlled HIV on antiretroviral therapy
             (ART), per study criteria.

        Exclusion Criteria:

          -  Has had chemotherapy, definitive radiation, or biological cancer therapy within 4
             weeks (2 weeks for palliative radiation) prior to the first dose of study intervention
             or has not recovered from any adverse events (AEs) that were due to cancer
             therapeutics administered more than 4 weeks earlier. Participants receiving ongoing
             replacement hormone therapy for endocrine immune-related AEs will not be excluded from
             participation in this study.

          -  Has a history of a second malignancy, unless potentially curative treatment has been
             completed with no evidence of malignancy for 2 years. The time requirement does not
             apply to participants who underwent successful definitive resection of basal cell
             carcinoma of the skin, superficial bladder cancer or in situ cervical cancer, or other
             in-situ cancers.

          -  Has clinically active central nervous system metastases and/or carcinomatous
             meningitis.

          -  Has had a severe hypersensitivity reaction to treatment with the monoclonal
             antibody/components of the study intervention or has a history of any contraindication
             or has a severe hypersensitivity to any components of pembrolizumab (≥Grade 3).

          -  Has an active infection requiring therapy.

          -  Has a history of (noninfectious) pneumonitis that required steroids or current
             pneumonitis.

          -  Has an active autoimmune disease that has required systemic treatment in the past 2
             years except vitiligo or resolved childhood asthma/atopy.

          -  Is on chronic systemic steroid therapy in excess of replacement doses (prednisone ≤10
             mg/day is acceptable), or on any other form of immunosuppressive medication.

          -  Participants with known Hepatitis B or C infections or known to be positive for
             hepatitis B antigen/hepatitis B virus DNA or hepatitis C antibody or RNA.

          -  HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric
             Castleman's Disease.

          -  Has a known psychiatric or substance abuse disorder that would interfere with the
             participant's ability to cooperate with the requirements of the study.

          -  Is pregnant or breastfeeding or expecting to conceive or father children within the
             projected duration of the study, starting with the screening visit through 120 days
             after the last dose of study intervention.

          -  Has not fully recovered from any effects of major surgery without significant
             detectable infection.

          -  Has received a live-virus vaccine within 30 days of planned treatment start.

          -  Is currently participating and receiving study intervention in a study of an
             investigational agent or has participated and received study intervention in a study
             of an investigational agent or has used an investigational device within 28 days of
             administration of V938.

          -  Has a history of re-irradiation for HNSCC at the projected injection site.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants Who Experience Dose-Limiting Toxicity (DLT)
Time Frame:Up to 42 days
Safety Issue:
Description:The number of participants experiencing toxicities that are possibly, probably, or definitely related to study intervention administration will be reported.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Up to 2 years
Safety Issue:
Description:ORR is defined as the percentage of participants who have 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), as assessed by the investigator. In solid tumors, assessment will be based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) and modified RECIST 1.1 for immune-based therapeutics (iRECIST). The percentage of participants who experience a CR or PR based on the above criteria will be presented.
Measure:Area Under the Concentration-Time Curve from 0 to Infinity (AUC0-inf) for V938 Ribonucleic Acid (RNA) in Plasma
Time Frame:Predose cycle 1 on 4 separate days, cycles 2, 3, 5, 8, 9, and 10 on day 1. 2, 4, and 6 hours postdose cycle 1 on 2 separate days, and cycle 2 on day 1. 2-4 hours postdose cycle 3 on day 1. 30 days after last dose. Each cycle is 21 days.
Safety Issue:
Description:The AUC0-inf for V938 RNA in plasma will be calculated.
Measure:Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) Reached in Plasma
Time Frame:Predose cycle 1 on 4 separate days, cycles 2, 3, 5, 8, 9, and 10 on day 1. 2, 4, and 6 hours postdose cycle 1 on 2 separate days, and cycle 2 on day 1. 2-4 hours postdose cycle 3 on day 1. 30 days after last dose. Each cycle is 21 days.
Safety Issue:
Description:The Cmax for V938 RNA in plasma will be reported.
Measure:V938 Excretion: Polymerase Chain Reaction (PCR)
Time Frame:Predose cycle 1 on 3 separate days, and cycles 3, 5, 8, 9, and 10 on day 1. 2, 4, and 6 hours postdose cycle 1 day 1. Each cycle is 21 days.
Safety Issue:
Description:The presence of V938, determined by PCR, in oral cavity/throat, urine, injection site, and anus will be reported.
Measure:V938 Excretion: Infectivity
Time Frame:Predose cycle 1 on 3 separate days, and cycles 3, 5, 8, 9, and 10 on day 1. 2, 4, and 6 hours postdose cycle 1 day 1. Each cycle is 21 days.
Safety Issue:
Description:The presence of V938, determined by infectivity of V938, in oral cavity/throat, urine, injection site, and anus will be reported.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • Programmed Cell Death-1 (PD1, PD-1)
  • Programmed Death-Ligand 1 (PDL1, PD-L1)

Last Updated

April 9, 2020