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Evaluating pembrolizumab alone or with other treatments for advanced melanoma

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 (KEYMAKER-U02): Substudy 02B

Phase1; Phase2 Interventional Merck Sharp & Dohme LLC · NCT04305054

This study is testing if the drug pembrolizumab, alone or with other new treatments, can help people with untreated advanced melanoma by shrinking their tumors and seeing how well they tolerate the treatment.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment315 (estimated)
Ages18 Years to 120 Years
SexAll
SponsorMerck Sharp & Dohme LLC Industry-sponsored
Drugs / interventionsLenvatinib, pembrolizumab, Vibostolimab, Quavonlimab, Favezelimab, chemotherapy
Locations60 sites (Los Angeles, California and 59 other locations)
Trial IDNCT04305054 on ClinicalTrials.gov

What this trial studies

This study investigates the safety and efficacy of pembrolizumab, both alone and in combination with investigational agents, for patients with untreated advanced melanoma. Participants will receive either pembrolizumab alone or in combination with other treatments like vibostolimab or lenvatinib. The study aims to assess how well these treatments work in shrinking tumors and how well patients tolerate them. The research includes multiple treatment arms, with some participants transitioning to pembrolizumab monotherapy based on their response to treatment.

Who should consider this trial

Good fit: Ideal candidates are individuals with unresectable Stage III or IV melanoma who have not received prior treatment for their advanced disease.

Not a fit: Patients with resectable melanoma or those who have previously received treatment for advanced melanoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide new effective treatment options for patients with advanced melanoma.

How similar studies have performed: Other studies have shown promising results with pembrolizumab and similar immunotherapy approaches, indicating potential for success in this study.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Has histologically or cytologically confirmed melanoma
* Has unresectable Stage III or Stage IV melanoma, not amenable to local therapy
* Has been untreated for advanced disease.
* Has provided a tumor biopsy
* If capable of producing sperm, male participants agree to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention (7 days):

  * Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR
  * Uses contraception unless confirmed to be azoospermic
* A 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 WOCBP OR
  * Is a WOCBP and Uses a contraceptive method that is highly effective, with low user dependency, or be abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:
  * MK-4280A: 120 days
  * MK-1308A: 120 days
  * MK-7684: 50 days
  * MK-3475: 120 days
  * Lenvatinib: 30 days
  * ATRA: 30 days
* Has adequate organ function
* Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia and Grade 2 neuropathy)

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 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 history of Hepatitis B or known Hepatitis C virus infection
* 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 known psychiatric or substance abuse disorder that would interfere with requirements of the study
* Participants who receive lenvatinib have the following additional exclusion criteria:

  * Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula
  * Has radiographic evidence of encasement of invasion of a 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
  * Has urine protein ≥1 g/24-hour.
  * Has presence of gastrointestinal condition including malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib

Where this trial is running

Los Angeles, California and 59 other locations

+10 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Melanomaprogrammed cell death 1programmed cell death ligand 1T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine receptor motif domainsCytotoxic T lymphocyte associated protein 4
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.