Substudy 02B: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With First Line (1L) Advanced Melanoma (MK-3475-02B/KEYMAKER-U02)

NCT ID: NCT04305054

Last Updated: 2025-08-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

315 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-01

Study Completion Date

2026-04-20

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Substudy 02B is part of a larger research study where researchers are looking for new ways to treat advanced melanoma that has not been treated before. The larger study is the umbrella study. Researchers want to know if adding other treatments to pembrolizumab can treat advanced melanoma. The goals of this study are to learn:

* About the safety and how well people tolerate pembrolizumab given with other treatments
* How many people have melanoma that responds (gets smaller or goes away) to treatment

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

With Amendment 6, all arms are closed to enrollment. Participants in arms 2 (pembrolizumab), 3 (coformulation pembrolizumab/quavonlimab), and 4 (coformulation pembrolizumab/quavonlimab + lenvatinib) who complete study treatment or otherwise meet end of treatment (EOT) criteria will be discontinued from the study after completing the EOT visit and any required safety follow-up visits. Participants in arm 6 (coformulation favezelimab/pembrolizumab + All-trans Retinoic Acid \[ATRA\]) will discontinue ATRA and participants in arms 5 and 6 can continue on coformulation favezelimab/pembrolizumab or pembrolizumab.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Melanoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Pembrolizumab + Vibostolimab

Participants will receive pembrolizumab intravenously (IV) plus vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

Administered via IV infusion at a specified dose on specified days

Vibostolimab

Intervention Type BIOLOGICAL

Administered via IV infusion at a specified dose on specified days

Pembrolizumab

Participants will receive pembrolizumab IV at a specified dose on specified days for a total treatment duration of up to approximately 2 years.

Group Type ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type BIOLOGICAL

Administered via IV infusion at a specified dose on specified days

Coformulation Pembrolizumab/Quavonlimab

Participants will receive coformulation of pembrolizumab and quavonlimab (MK-1308A) IV at a specified dose on specified days for a total treatment duration of up to approximately 2 years.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

Administered via IV infusion at a specified dose on specified days

Pembrolizumab/Quavonlimab

Intervention Type BIOLOGICAL

Administered via IV infusion at a specified dose on specified days

Coformulation Pembrolizumab/Quavonlimab + Lenvatinib

Participants will receive coformulation of pembrolizumab and quavonlimab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

Administered via IV infusion at a specified dose on specified days

Pembrolizumab/Quavonlimab

Intervention Type BIOLOGICAL

Administered via IV infusion at a specified dose on specified days

Lenvatinib

Intervention Type DRUG

Administered via oral capsule at a specified dose on specified days

Coformulation Favezelimab/Pembrolizumab

Participants will receive cofomulation of favezelimab + pembrolizumab (MK-4280A) IV at specified dose on specified days every 3 weeks (Q3W) for up to approximately 2 years

Group Type EXPERIMENTAL

Favezelimab/Pembrolizumab

Intervention Type BIOLOGICAL

Administered via IV infusion at a specified dose on specified days

Coformulation Favezelimab/Pembrolizumab + All-trans Retinoic Acid (ATRA)

Participants will receive coformulation of favezelimab and pembrolizumab IV Q3W for up to 35 cycles, plus ATRA orally (for 3 days surrounding each infusion of MK-4280A, including Days 1, 2, and 3 of Cycle 1 and on Days -1, 1, and 2 of all subsequent cycles).

Group Type EXPERIMENTAL

ATRA

Intervention Type DRUG

Administered via oral capsule at a specified dose on specified days

Coformulation Favezelimab/Pembrolizumab + Vibostolimab

Participants will receive coformulation of favezelimab and pembrolizumab (MK-4280A) IV and vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.

Group Type EXPERIMENTAL

Vibostolimab

Intervention Type BIOLOGICAL

Administered via IV infusion at a specified dose on specified days

Favezelimab/Pembrolizumab

Intervention Type BIOLOGICAL

Administered via IV infusion at a specified dose on specified days

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Pembrolizumab

Administered via IV infusion at a specified dose on specified days

Intervention Type BIOLOGICAL

Vibostolimab

Administered via IV infusion at a specified dose on specified days

Intervention Type BIOLOGICAL

Pembrolizumab/Quavonlimab

Administered via IV infusion at a specified dose on specified days

Intervention Type BIOLOGICAL

Lenvatinib

Administered via oral capsule at a specified dose on specified days

Intervention Type DRUG

Favezelimab/Pembrolizumab

Administered via IV infusion at a specified dose on specified days

Intervention Type BIOLOGICAL

ATRA

Administered via oral capsule at a specified dose on specified days

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

MK-3475 KEYTRUDA® MK-7684 MK-1308A MK-7902 E7080 LENVIMA® MK-4280A

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

The Angeles Clinic and Research Institute ( Site 2009)

Los Angeles, California, United States

Site Status

UCLA Hematology & Oncology ( Site 2004)

Los Angeles, California, United States

Site Status

Providence Saint John's Health Center ( Site 2010)

Santa Monica, California, United States

Site Status

University of Colorado, Anschutz Cancer Pavilion ( Site 2012)

Aurora, Colorado, United States

Site Status

University of Florida College of Medicine-UF Health Cancer Center/Clinical Trials Office ( Site 2026)

Gainesville, Florida, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 2022)

Baltimore, Maryland, United States

Site Status

R.J. Zuckerberg Cancer Center ( Site 2032)

Lake Success, New York, United States

Site Status

NYU Clinical Cancer Center ( Site 2002)

New York, New York, United States

Site Status

Duke Cancer Institute ( Site 2005)

Durham, North Carolina, United States

Site Status

Martha Morehouse Tower ( Site 2020)

Columbus, Ohio, United States

Site Status

Oregon Health & Science University ( Site 2013)

Portland, Oregon, United States

Site Status

University of Pennsylvania Abramson Cancer Center ( Site 2008)

Philadelphia, Pennsylvania, United States

Site Status

West Cancer Center - East Campus ( Site 2014)

Germantown, Tennessee, United States

Site Status

Mays Cancer Center ( Site 2025)

San Antonio, Texas, United States

Site Status

Inova Schar Cancer Institute ( Site 2011)

Fairfax, Virginia, United States

Site Status

Clinica Adventista Belgrano-Oncology ( Site 2242)

Caba., Buenos Aires, Argentina

Site Status

Instituto Alexander Fleming-Alexander Fleming ( Site 2243)

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

Sanatorio Finochietto ( Site 2245)

Buenos Aires, , Argentina

Site Status

Calvary Mater Newcastle-Medical Oncology ( Site 2404)

Waratah, New South Wales, Australia

Site Status

Melanoma Institute Australia ( Site 2402)

Wollstonecraft, New South Wales, Australia

Site Status

Tasman Oncology Research Pty Ltd ( Site 2403)

Southport, Queensland, Australia

Site Status

Fiona Stanley Hospital ( Site 2401)

Murdoch, Western Australia, Australia

Site Status

IC La Serena Research ( Site 2254)

La Serena, Coquimbo Region, Chile

Site Status

FALP-UIDO ( Site 2251)

Santiago, Region M. de Santiago, Chile

Site Status

Oncovida ( Site 2257)

Santiago, Region M. de Santiago, Chile

Site Status

Bradfordhill ( Site 2252)

Santiago, Region M. de Santiago, Chile

Site Status

CIDO SpA-Oncology ( Site 2256)

Temuco, Región de la Araucanía, Chile

Site Status

Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia-Center Investigator ( Site 2261)

Bogotá, Bogota D.C., Colombia

Site Status

Fundación Valle del Lili ( Site 2265)

Cali, Valle del Cauca Department, Colombia

Site Status

Hopital La Timone ( Site 2103)

Marseille, Bouches-du-Rhone, France

Site Status

CHU de Bordeaux- Hopital Saint Andre ( Site 2108)

Bordeaux, Gironde, France

Site Status

Institut Claudius Regaud ( Site 2105)

Toulouse, Haute-Garonne, France

Site Status

C.H. Lyon Sud ( Site 2102)

Pierre-Bénite, Rhone, France

Site Status

A.P.H. Paris, Hopital Saint Louis ( Site 2107)

Paris, , France

Site Status

Gustave Roussy ( Site 2101)

Villejuif, Île-de-France Region, France

Site Status

General Hospital of Athens "Laiko"-First Department of Internal Medicine ( Site 2212)

Athens, Attica, Greece

Site Status

European Interbalkan Medical Center-Oncology Department ( Site 2211)

Thessaloniki, , Greece

Site Status

Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ ( Site 2221)

Szeged, Csongrád megye, Hungary

Site Status

HaEmek Medical Center ( Site 2703)

Afula, , Israel

Site Status

Rambam Health Care Campus-Oncology ( Site 2704)

Haifa, , Israel

Site Status

Hadassah Ein Karem Jerusalem ( Site 2702)

Jerusalem, , Israel

Site Status

Rabin Medical Center-Oncology ( Site 2705)

Petah Tikva, , Israel

Site Status

Chaim Sheba Medical Center ( Site 2701)

Ramat Gan, , Israel

Site Status

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 2399)

Milan, , Italy

Site Status

Istituto Europeo di Oncologia ( Site 2301)

Milan, , Italy

Site Status

Istituto Nazionale Tumori Fondazione Pascale ( Site 2302)

Napoli, , Italy

Site Status

Istituto Oncologico Veneto IRCCS ( Site 2355)

Padua, , Italy

Site Status

Policlinico Le Scotte - A.O. Senese ( Site 2377)

Siena, , Italy

Site Status

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie ( Site 2233)

Warsaw, Masovian Voivodeship, Poland

Site Status

Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 2231)

Gdansk, Pomeranian Voivodeship, Poland

Site Status

CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE ( Site 2865)

Port Elizabeth, Eastern Cape, South Africa

Site Status

Steve Biko Academic Hospital-Medical Oncology ( Site 2862)

Pretoria, Gauteng, South Africa

Site Status

LIFE GROENKLOOF-Mary Potter Cancer Centre ( Site 2861)

Pretoria, Gauteng, South Africa

Site Status

Sandton Oncology Medical Group (Pty) Ltd-Research ( Site 2863)

Sandton, Gauteng, South Africa

Site Status

Cape Town Oncology Trials ( Site 2864)

Cape Town, Western Cape, South Africa

Site Status

HOSPITAL CLÍNIC DE BARCELONA-ICHMO- Clinic Institut of Haematological and Oncological diseases ( Site 2801)

Barcelona, Catalonia, Spain

Site Status

Hospital Universitario Ramón y Cajal ( Site 2802)

Madrid, Madrid, Comunidad de, Spain

Site Status

Hôpitaux Universitaires de Genève (HUG)-Oncology ( Site 2603)

Geneva, Canton of Geneva, Switzerland

Site Status

CHUV Centre Hospitalier Universitaire Vaudois ( Site 2602)

Lausanne, Canton of Vaud, Switzerland

Site Status

Universitaetsspital Zuerich ( Site 2601)

Zuerich Flughafen, Canton of Zurich, Switzerland

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Argentina Australia Chile Colombia France Greece Hungary Israel Italy Poland South Africa Spain Switzerland

Related Links

Access external resources that provide additional context or updates about the study.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

MK-3475-02B

Identifier Type: OTHER

Identifier Source: secondary_id

KEYMAKER-U02

Identifier Type: OTHER

Identifier Source: secondary_id

2023-506313-21-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1293-5644

Identifier Type: REGISTRY

Identifier Source: secondary_id

2019-003977-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

3475-02B

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Phase Ib of L-NMMA and Pembrolizumab
NCT03236935 ACTIVE_NOT_RECRUITING PHASE1
A Beta-only IL-2 ImmunoTherapY Study
NCT05086692 RECRUITING PHASE1/PHASE2