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)

Completed · Phase 1/Phase 2

Conditions studied: Melanoma

In brief

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. As of Amendment 4 (effective date: 05JAN2022), a third arm has been opened to participant enrollment, treatment with pembrolizumab and all-trans retinoic acid (ATRA). Enrollment into the first two arms, treatment with pembrolizumab + quavonlimab+ vibostolimab and treatment with pembrolizumab + quavonlimab + lenvatinib has been completed per protocol as of September 2021.

Key facts

Study ID: NCT04305041
Run by: Merck Sharp & Dohme LLC
People needed: 100
Starts: 2020-06-26
Expected to finish: 2025-08-25
Last updated by the study team: 2025-08-29

Who can join

Age: 18 and older, up to 120. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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)

You may not qualify if…

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

Where it is running

The Angeles Clinic and Research Institute ( Site 1009) — Los Angeles, California, United States
UCLA Hematology & Oncology ( Site 1004) — Los Angeles, California, United States
Providence Saint John's Health Center ( Site 1010) — Santa Monica, California, United States
University of Colorado, Anschutz Cancer Pavilion ( Site 1012) — Aurora, Colorado, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 1022) — Baltimore, Maryland, United States
NYU Clinical Cancer Center ( Site 1002) — New York, New York, United States
Duke Cancer Institute ( Site 1005) — Durham, North Carolina, United States
Martha Morehouse Tower ( Site 1020) — Columbus, Ohio, United States
Oregon Health & Science University ( Site 1013) — Portland, Oregon, United States
University of Pennsylvania Abramson Cancer Center ( Site 1008) — Philadelphia, Pennsylvania, United States
West Cancer Center - East Campus ( Site 1014) — Germantown, Tennessee, United States
University of Texas MD Anderson Cancer Center ( Site 1006) — Houston, Texas, United States
Inova Schar Cancer Institute ( Site 1011) — Fairfax, Virginia, United States
Calvary Mater Newcastle-Medical Oncology ( Site 1404) — Waratah, New South Wales, Australia
Melanoma Institute Australia ( Site 1402) — Wollstonecraft, New South Wales, Australia
Tasman Oncology Research Pty Ltd ( Site 1403) — Southport, Queensland, Australia
Fiona Stanley Hospital ( Site 1401) — Murdoch, Western Australia, Australia
Hopital La Timone ( Site 1103) — Marseille, Bouches-du-Rhone, France
Hopital Saint Andre ( Site 1108) — Bordeaux, Gironde, France
Institut Claudius Regaud ( Site 1105) — Toulouse, Haute-Garonne, France
Centre Hospitalier Lyon Sud ( Site 1102) — Pierre-Bénite, Rhone, France
A.P.H. Paris, Hopital Saint Louis ( Site 1107) — Paris, France
Gustave Roussy ( Site 1101) — Villejuif, Île-de-France Region, France
HaEmek Medical Center ( Site 1703) — Afula, Israel
Rambam Health Care Campus-Oncology ( Site 1704) — Haifa, Israel

Full record on ClinicalTrials.gov

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