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)

NCT04305054 | Active Not Recruiting Phase 1 FDA Drug

• 6 other identifiers: 3475-02BMK-3475-02BKEYMAKER-U022023-506313-21-00U1111-1293-56442019-003977-24
• Study Type: interventional
• Target: 315
• Locations: 14 countries
• Sites: 60

Brief Summary

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

Conditions

Melanoma

Keywords

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); Cytotoxic T lymphocyte associated protein 4 (CTLA4)

Outcome Measures

Primary Outcomes (6)

• Percentage of participants who experience a dose-limiting toxicity (DLT): Safety lead-in phase

  The percentage of participants who experience 1 or more protocol-defined DLTs during the safety lead-in period will be reported.

  Up to ~3 weeks

• Percentage of participants who experience an adverse event (AE): Safety lead-in

  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 during the safety lead-in period will be reported.

  Up to ~3 weeks

• Percentage of participants who discontinue study treatment due to an AE: Safety lead-in

  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 discontinue study treatment due to an AE during the safety lead-in will be reported.

  Up to ~3 weeks

• Percentage of participants who experience an adverse event (AE)

  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.

  Up to ~28 months

• Percentage of participants who discontinue study treatment due to an AE

  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 discontinue study treatment due to an AE will be reported.

  Up to ~24 months

• Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)

  ORR is defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by blinded independent central review (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.

  Up to ~30 months

Secondary Outcomes (1)

• Duration of Response (DOR) per RECIST 1.1

  Up to ~30 months

Study Arms (7)

Pembrolizumab + Vibostolimab

EXPERIMENTAL

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.

Biological: Pembrolizumab; Biological: Vibostolimab

Pembrolizumab

ACTIVE COMPARATOR

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

Biological: Pembrolizumab

Coformulation Pembrolizumab/Quavonlimab

EXPERIMENTAL

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.

Biological: Pembrolizumab; Biological: Pembrolizumab/Quavonlimab

Coformulation Pembrolizumab/Quavonlimab + Lenvatinib

EXPERIMENTAL

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.

Biological: Pembrolizumab; Biological: Pembrolizumab/Quavonlimab; Drug: Lenvatinib

Coformulation Favezelimab/Pembrolizumab

EXPERIMENTAL

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

Biological: Favezelimab/Pembrolizumab

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

EXPERIMENTAL

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).

Drug: ATRA

Coformulation Favezelimab/Pembrolizumab + Vibostolimab

EXPERIMENTAL

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.

Biological: Vibostolimab; Biological: Favezelimab/Pembrolizumab

Interventions

Vibostolimab BIOLOGICAL

Administered via IV infusion at a specified dose on specified days

Also known as: MK-7684

Coformulation Favezelimab/Pembrolizumab + Vibostolimab; Pembrolizumab + Vibostolimab

Pembrolizumab/Quavonlimab BIOLOGICAL

Administered via IV infusion at a specified dose on specified days

Also known as: MK-1308A

Coformulation Pembrolizumab/Quavonlimab; Coformulation Pembrolizumab/Quavonlimab + Lenvatinib

Lenvatinib DRUG

Administered via oral capsule at a specified dose on specified days

Also known as: MK-7902, E7080, LENVIMA®

Coformulation Pembrolizumab/Quavonlimab + Lenvatinib

Favezelimab/Pembrolizumab BIOLOGICAL

Administered via IV infusion at a specified dose on specified days

Also known as: MK-4280A

Coformulation Favezelimab/Pembrolizumab; Coformulation Favezelimab/Pembrolizumab + Vibostolimab

ATRA DRUG

Administered via oral capsule at a specified dose on specified days

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

Pembrolizumab BIOLOGICAL

Administered via IV infusion at a specified dose on specified days

Also known as: MK-3475, KEYTRUDA®

Coformulation Pembrolizumab/Quavonlimab; Coformulation Pembrolizumab/Quavonlimab + Lenvatinib; Pembrolizumab; Pembrolizumab + Vibostolimab

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

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 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (60)

The Angeles Clinic and Research Institute ( Site 2009)

Los Angeles, California, 90025, United States

Location

UCLA Hematology & Oncology ( Site 2004)

Los Angeles, California, 90095, United States

Location

Providence Saint John's Health Center ( Site 2010)

Santa Monica, California, 90404, United States

Location

University of Colorado, Anschutz Cancer Pavilion ( Site 2012)

Aurora, Colorado, 80045, United States

Location

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

Gainesville, Florida, 32608, United States

Location

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

Baltimore, Maryland, 21287, United States

Location

R.J. Zuckerberg Cancer Center ( Site 2032)

Lake Success, New York, 11042, United States

Location

NYU Clinical Cancer Center ( Site 2002)

New York, New York, 10016, United States

Location

Duke Cancer Institute ( Site 2005)

Durham, North Carolina, 27710, United States

Location

Martha Morehouse Tower ( Site 2020)

Columbus, Ohio, 43221, United States

Location

Oregon Health & Science University ( Site 2013)

Portland, Oregon, 97239, United States

Location

University of Pennsylvania Abramson Cancer Center ( Site 2008)

Philadelphia, Pennsylvania, 19104, United States

Location

West Cancer Center - East Campus ( Site 2014)

Germantown, Tennessee, 38138, United States

Location

Mays Cancer Center ( Site 2025)

San Antonio, Texas, 78229, United States

Location

Inova Schar Cancer Institute ( Site 2011)

Fairfax, Virginia, 22031, United States

Location

Clinica Adventista Belgrano-Oncology ( Site 2242)

Caba., Buenos Aires, C1430EGF, Argentina

Location

Instituto Alexander Fleming-Alexander Fleming ( Site 2243)

Buenos Aires, Buenos Aires F.D., 1426ANZ, Argentina

Location

Sanatorio Finochietto ( Site 2245)

Buenos Aires, C1187AAN, Argentina

Location

Calvary Mater Newcastle-Medical Oncology ( Site 2404)

Waratah, New South Wales, 2298, Australia

Location

Melanoma Institute Australia ( Site 2402)

Wollstonecraft, New South Wales, 2065, Australia

Location

Tasman Oncology Research Pty Ltd ( Site 2403)

Southport, Queensland, 4120, Australia

Location

Fiona Stanley Hospital ( Site 2401)

Murdoch, Western Australia, 6150, Australia

Location

IC La Serena Research ( Site 2254)

La Serena, Coquimbo Region, 1720430, Chile

Location

FALP-UIDO ( Site 2251)

Santiago, Region M. de Santiago, 7500921, Chile

Location

Oncovida ( Site 2257)

Santiago, Region M. de Santiago, 7500994, Chile

Location

Bradfordhill ( Site 2252)

Santiago, Region M. de Santiago, 8420383, Chile

Location

CIDO SpA-Oncology ( Site 2256)

Temuco, Región de la Araucanía, 4810218, Chile

Location

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

Bogotá, Bogota D.C., 111321, Colombia

Location

Fundación Valle del Lili ( Site 2265)

Cali, Valle del Cauca Department, 760032, Colombia

Location

Hopital La Timone ( Site 2103)

Marseille, Bouches-du-Rhone, 13005, France

Location

CHU de Bordeaux- Hopital Saint Andre ( Site 2108)

Bordeaux, Gironde, 33075, France

Location

Institut Claudius Regaud ( Site 2105)

Toulouse, Haute-Garonne, 31059, France

Location

C.H. Lyon Sud ( Site 2102)

Pierre-Bénite, Rhone, 69495, France

Location

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

Paris, 75010, France

Location

Gustave Roussy ( Site 2101)

Villejuif, Île-de-France Region, 94805, France

Location

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

Athens, Attica, 115 26, Greece

Location

European Interbalkan Medical Center-Oncology Department ( Site 2211)

Thessaloniki, 570 01, Greece

Location

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

Szeged, Csongrád megye, 6720, Hungary

Location

HaEmek Medical Center ( Site 2703)

Afula, 1834111, Israel

Location

Rambam Health Care Campus-Oncology ( Site 2704)

Haifa, 3109601, Israel

Location

Hadassah Ein Karem Jerusalem ( Site 2702)

Jerusalem, 9112001, Israel

Location

Rabin Medical Center-Oncology ( Site 2705)

Petah Tikva, 4941492, Israel

Location

Chaim Sheba Medical Center ( Site 2701)

Ramat Gan, 5265601, Israel

Location

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

Milan, 20133, Italy

Location

Istituto Europeo di Oncologia ( Site 2301)

Milan, 20141, Italy

Location

Istituto Nazionale Tumori Fondazione Pascale ( Site 2302)

Naples, 80131, Italy

Location

Istituto Oncologico Veneto IRCCS ( Site 2355)

Padova, 35128, Italy

Location

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

Siena, 53100, Italy

Location

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

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

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

Gdansk, Pomeranian Voivodeship, 80-952, Poland

Location

CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE ( Site 2865)

Port Elizabeth, Eastern Cape, 6055, South Africa

Location

Steve Biko Academic Hospital-Medical Oncology ( Site 2862)

Pretoria, Gauteng, 0002, South Africa

Location

LIFE GROENKLOOF-Mary Potter Cancer Centre ( Site 2861)

Pretoria, Gauteng, 0181, South Africa

Location

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

Sandton, Gauteng, 2196, South Africa

Location

Cape Town Oncology Trials ( Site 2864)

Cape Town, Western Cape, 7570, South Africa

Location

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

Barcelona, Catalonia, 08036, Spain

Location

Hospital Universitario Ramón y Cajal ( Site 2802)

Madrid, Madrid, Comunidad de, 28034, Spain

Location

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

Geneva, Canton of Geneva, 1211, Switzerland

Location

CHUV Centre Hospitalier Universitaire Vaudois ( Site 2602)

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Universitaetsspital Zuerich ( Site 2601)

Zuerich Flughafen, Canton of Zurich, 8058, Switzerland

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Melanoma; Parkinson Disease 4, Autosomal Dominant Lewy Body; Diabetes Mellitus, Insulin-Dependent, 12

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: March 12, 2020
• Study Start: July 1, 2020
• Primary Completion (Estimated): May 20, 2026
• Study Completion (Estimated): May 20, 2026
• Last Updated: April 8, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

CL (5); AR (3); PL (2); ZA (5); AU (4); US (15); ES (2); CO (2); CH (3); IL (5); GR (2); FR (6); IT (5); HU (1)