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/KEYMAKER-U02)

  • End date
    Apr 3, 2030
  • participants needed
  • sponsor
    Merck Sharp & Dohme LLC
Updated on 13 July 2022
metastatic melanoma
advanced melanoma
immunologic adjuvant


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.

Condition Melanoma
Treatment Pembrolizumab, ATRA, Lenvatinib, MK-7684, MK-1308, vibostolimab, Guavonlimab, Quavonlimab
Clinical Study IdentifierNCT04305041
SponsorMerck Sharp & Dohme LLC
Last Modified on13 July 2022


Yes No Not Sure

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 imaging documenting progression per RECIST 1.1 and iRECIST after initiation of an anti-PD-1/L1 agent, or by RECIST 1.1 if progression occurred on adjuvant therapy or in the setting of rapid progression
Has not received more than 3 lines of therapy for their advanced melanoma
Has provided a tumor biopsy
Male participants who receive lenvatinib or ATRA are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 7 days after the last dose of lenvatinib or ATRA; for male participants who only receive pembrolizumab, quavonlimab, vibostolimab, 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, quavonlimab, vibostolimab or 30 days after the last dose of lenvatinib or ATRA, 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
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Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

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