Clinical Trials /

Substudy 02A: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents in Participants With Programmed Cell-death 1 (PD-1) Refractory Melanoma (MK-3475-02A)

NCT04305041

Description:

Substudy 02A 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 02A is to evaluate the safety and efficacy of investigational treatment arms in participants with PD-1 refractory melanoma 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 02A: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents in Participants With Programmed Cell-death 1 (PD-1) Refractory Melanoma (MK-3475-02A)
  • 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 02A

Clinical Trial IDs

  • ORG STUDY ID: 3475-02A
  • SECONDARY ID: 2019-003956-35
  • SECONDARY ID: MK-3475-02A
  • NCT ID: NCT04305041

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
PembrolizumabMK-3475, KEYTRUDA®Pembrolizumab + MK-1308 + Lenvatinib
MK-1308Pembrolizumab + MK-1308 + Lenvatinib
MK-7684Pembrolizumab + MK-1308 + MK-7684
LenvatinibMK-7902, LENVIMA®Pembrolizumab + MK-1308 + Lenvatinib

Purpose

Substudy 02A 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 02A is to evaluate the safety and efficacy of investigational treatment arms in participants with PD-1 refractory melanoma 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-1308 + MK-7684ExperimentalParticipants will receive pembrolizumab intravenously (IV) plus MK-1308 IV plus MK-7684 IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.
  • Pembrolizumab
  • MK-1308
  • MK-7684
Pembrolizumab + MK-1308 + LenvatinibExperimentalParticipants will receive pembrolizumab IV plus MK-1308 IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
  • Pembrolizumab
  • MK-1308
  • Lenvatinib

Eligibility Criteria

        Inclusion Criteria:

          -  Has histologically or cytologically confirmed melanoma

          -  Has unresectable Stage III or Stage IV melanoma, not amenable to local therapy

          -  Has progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb)
             administered either as monotherapy, or in combination with other therapies

          -  Has submitted prestudy imaging

          -  Has not received more than 3 lines of therapy for their advanced melanoma

          -  Has provided a tumor biopsy

          -  Male participants who receive lenvatinib are abstinent from heterosexual intercourse
             or agree to use contraception during the intervention period and for at least 5 days
             after the last dose of lenvatinib; for male participants who only receive
             pembrolizumab, MK-1308, MK-7684, or a combination, no contraception measures are
             needed

          -  Female participant 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-1308, MK-7684 or 30 days
             after the last dose of lenvatinib, 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 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 a pre-existing Grade ≥3 gastrointestinal fistula or nongastrointestinal fistula

          -  Has radiographic evidence of encasement of invasion of major blood vessel or of
             intratumoral cavitation

          -  Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the
             first dose of study intervention

          -  Has clinically significant cardiovascular disease within 12 months from first dose of
             study intervention
      
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 ~28 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:Duration of Response (DOR) per RECIST 1.1
Time Frame:Up to ~30 months
Safety Issue:
Description:For participants in the analysis population who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters), DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 as assessed by BICR. 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.

Details

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

Trial Keywords

  • receptor tyrosine kinase inhibitor
  • programmed cell death 1 (PD-1, PD1)
  • programmed cell death ligand 1 (PD-L1, PDL1)
  • T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine receptor motif domains (TIGIT)

Last Updated

June 23, 2020