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Substudy 02C: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Stage III Melanoma Who Are Candidates for Neoadjuvant Therapy (MK-3475-02C)

NCT04303169

Description:

Substudy 02C is part of a larger research study that is testing experimental treatments for melanoma, a type of skin cancer. The larger study is the umbrella study. The goal of substudy 02C is to evaluate the safety and efficacy of investigational treatment arms in participants with Stage III melanoma who are candidates for neoadjuvant therapy to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Substudy 02C: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Stage III Melanoma Who Are Candidates for Neoadjuvant Therapy (MK-3475-02C)
  • Official Title: A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Participants With Melanoma: Substudy 02C

Clinical Trial IDs

  • ORG STUDY ID: 3475-02C
  • SECONDARY ID: 2019-003978-22
  • SECONDARY ID: MK-3475-02C
  • NCT ID: NCT04303169

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
PembrolizumabMK-3475, KEYTRUDA®Pembrolizumab
MK-7684Pembrolizumab + MK-7684
V937Coxsackievirus A21 (CVA21), Formerly known as CAVATAK®, CAV21Pembrolizumab + V937

Purpose

Substudy 02C is part of a larger research study that is testing experimental treatments for melanoma, a type of skin cancer. The larger study is the umbrella study. The goal of substudy 02C is to evaluate the safety and efficacy of investigational treatment arms in participants with Stage III melanoma who are candidates for neoadjuvant therapy to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available.

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab + MK-7684ExperimentalPrior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab intravenously (IV) plus MK-7684 IV at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days. Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.
  • Pembrolizumab
  • MK-7684
Pembrolizumab + V937ExperimentalPrior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV plus V937 intratumorally (IT) at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days. Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.
  • Pembrolizumab
  • V937
PembrolizumabExperimentalPrior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days. Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Has histologically or cytologically confirmed melanoma

          -  Has clinically detectable and resectable Stage IIIB or IIIC or IIID melanoma amenable
             to surgery

          -  Has been untreated for Stage IIIB, IIIC or IIID melanoma

               -  surgical resection of primary melanoma is allowed

               -  prior radiotherapy to the primary melanoma is allowed

          -  Has provided a baseline tumor biopsy

          -  Male participants who receive V937 are abstinent from heterosexual intercourse or
             agree to use contraception during the intervention period and for at least 120 days
             after the last dose of V937

          -  Female participants are not pregnant or breastfeeding and are either not a woman of
             child-bearing potential (WOCBP) OR use a contraceptive method that is highly effective
             or are abstinent from heterosexual intercourse during the intervention period and for
             at least 120 days after the last dose of pembrolizumab, MK-7684, V937, whichever
             occurs last

          -  Has adequate organ function

          -  Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less
             (except alopecia)

        Exclusion Criteria:

          -  Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7
             days before the first dose of study intervention

          -  Has a known additional malignancy that is progressing or requires active treatment
             within the past 2 years

          -  Has known central nervous system (CNS) metastases and/or carcinomatous meningitis

          -  Has ocular or mucosal melanoma

          -  Has known hypersensitivity including previous clinically significant hypersensitivity
             reaction to treatment with another monoclonal antibody (mAb)

          -  Has an active autoimmune disease that has required systemic treatment in the past 2
             years

          -  Has an active infection requiring systemic therapy

          -  Has known history of human immunodeficiency virus (HIV)

          -  Has known history of hepatitis B

          -  Has a history of (noninfectious) pneumonitis

          -  Has a history of active tuberculosis (TB)

          -  Has received prior systemic anticancer therapy within 4 weeks prior to randomization

          -  Has received prior radiotherapy within 2 weeks of first dose of study intervention

          -  Has had major surgery <3 weeks prior to first dose of study intervention

          -  Has received a live vaccine within 30 days before the first dose of study intervention

          -  Has participated in a study of an investigational agent within 4 weeks prior to the
             first dose of study intervention

          -  Has had an allogeneic tissue/solid organ transplant

          -  Has only mucosal lesions

          -  Is not naïve to Talimogene laherparepvec (TVEC) and other oncolytic viruses
      
Maximum Eligible Age:120 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of participants who experience an adverse event (AE)
Time Frame:Up to ~16 months
Safety Issue:
Description:An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience an AE will be reported.

Secondary Outcome Measures

Measure:Near pathological complete response (near pCR) rate
Time Frame:Up to ~1.5 months
Safety Issue:
Description:Near pCR is defined as the proportion of participants with >0% but ≤10% of viable tumor cells in the treated tumor bed. Assessments are according to RECIST 1.1 by central review of the pathology results. RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Measure:Pathological partial response (pPR) rate
Time Frame:Up to ~1.5 months
Safety Issue:
Description:pPR rate is defined as the proportion of participants with >10% but ≤50% of the treated tumor bed occupied by viable tumor cells. Assessments are according to RECIST 1.1 by central review of the pathology results. RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Measure:Recurrence-free survival (RFS)
Time Frame:Up to ~65 months
Safety Issue:
Description:RFS is defined as the time from the date of surgery to (1) any recurrence (local, regional, or distant) as assessed by the investigator or (2) death due to any cause (both cancer and noncancer causes of death). Assessments are according to RECIST 1.1 which has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • programmed cell death 1 (PD-1, PD1)
  • programmed cell death ligand 1 (PD-L1, PDL1)
  • Coxsackievirus A21
  • Intracellular Adhesion Molecule-1 (ICAM-1)
  • T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine receptor motif domains (TIGIT)

Last Updated

June 23, 2020