Substudy 02D: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Melanoma Brain Metastasis (MK-3475-02D/KEYMAKER-U02)

NCT04700072 | Completed Phase 1 FDA Drug

• 6 other identifiers: 3475-02DMK-3475-02DKEYMAKER-U022023-506315-17-00U1111-1293-57042020-003742-36
• Study Type: interventional
• Target: 56
• Locations: 8 countries
• Sites: 36

Brief Summary

Substudy 02D 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 02D is to evaluate the safety and efficacy of investigational treatment arms in programmed cell-death 1 (PD-1) naïve or PD-1 exposed participants with melanoma brain metastasis (MBM) and to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available. As of amendment 2 (effective 01DEC2022) enrollment into the treatment arm of pembrolizumab and lenvatinib has been discontinued.

Conditions

Melanoma

Keywords

programmed cell death 1 (PD-1, PD1); programmed cell death ligand 1 (PD-L1, PDL1)

Outcome Measures

Primary Outcomes (3)

• 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 ≥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 (4)

• Duration of Response (DOR) per RECIST 1.1

  Up to ~30 months

• Brain metastasis response rate (BMRR) per Response Assessment in Neuro- Oncology Brain Metastases (RANO-BM)

  Up to ~30 months

• Brain metastasis duration of response (BM-DOR) per RANO-BM

  Up to ~30 months

• Progression-free survival (PFS) per RECIST 1.1

  Up to ~30 months

Study Arms (2)

Coformulation Pembrolizumab/Quavonlimab + Lenvatinib

EXPERIMENTAL

Participants will receive pembrolizumab/quavonlimab (coformulation of pembrolizumab and quavonlimab) intravenously (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

Pembrolizumab + Lenvatinib

EXPERIMENTAL

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

Biological: Pembrolizumab; Drug: Lenvatinib

Interventions

Pembrolizumab BIOLOGICAL

Administered via IV infusion at a specified dose on specified days

Also known as: MK-3475, KEYTRUDA®

Coformulation Pembrolizumab/Quavonlimab + Lenvatinib; Pembrolizumab + Lenvatinib

Pembrolizumab/Quavonlimab BIOLOGICAL

Administered via IV infusion at a specified dose on specified days

Also known as: MK-1308A

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; Pembrolizumab + Lenvatinib

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 American Joint Committee on Cancer (AJCC) Stage IV, M1D melanoma
• Is neurologically asymptomatic from brain metastases and has not received systemic corticosteroid therapy in the 10 days prior to beginning study intervention
• 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. The length of time required to continue contraception for each study intervention is:
• Lenvatinib: 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
• Female participants 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 or pembrolizumab/quavonlimab, or 30 days after the last dose of lenvatinib, whichever occurs last
• Has adequate organ function
• Female participants agree to abstain from breastfeeding during the study intervention period and for at least the time needed to eliminate study intervention after the last dose of study intervention. The length of time required for each study intervention is:
• MK-1308A: 120 days
• MK-3475: 120 days
• Lenvatinib: 30 days

You may not qualify if:

• Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 10 days before the first dose of study intervention
• Has current or history of known leptomeningeal involvement
• Has received stereotactic or highly conformal radiotherapy within 2 weeks before the start of dosing
• Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
• Has untreated or unresolved intracranial hemorrhage from central nervous system (CNS) metastasis
• Has an active infection requiring systemic therapy
• Has a known additional malignancy that is progressing or requires active treatment within the past 2 years
• Has ocular melanoma
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• Has known history of immunodeficiency virus (HIV)
• Has known history of hepatitis B or known hepatitis C virus
• Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis
• Has received prior systemic anticancer therapy within 4 weeks prior to randomization/allocation
• Has a history of whole brain irradiation
• Has received prior radiotherapy within 2 weeks of first dose of study intervention

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (36)

The Angeles Clinic and Research Institute ( Site 4009)

Los Angeles, California, 90025, United States

Location

UCLA Hematology & Oncology ( Site 4004)

Los Angeles, California, 90095, United States

Location

Providence Saint John's Health Center ( Site 4010)

Santa Monica, California, 90404, United States

Location

University of Colorado, Anschutz Cancer Pavilion ( Site 4012)

Aurora, Colorado, 80045, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 4022)

Baltimore, Maryland, 21287, United States

Location

NYU Clinical Cancer Center ( Site 4002)

New York, New York, 10016, United States

Location

Duke Cancer Institute ( Site 4005)

Durham, North Carolina, 27710, United States

Location

Martha Morehouse Tower ( Site 4020)

Columbus, Ohio, 43221, United States

Location

Inova Schar Cancer Institute ( Site 4011)

Fairfax, Virginia, 22031, United States

Location

Calvary Mater Newcastle ( Site 4404)

Waratah, New South Wales, 2298, Australia

Location

Melanoma Institute Australia ( Site 4402)

Wollstonecraft, New South Wales, 2065, Australia

Location

Hopital La Timone ( Site 4103)

Marseille, Bouches-du-Rhone, 13005, France

Location

CHU de Bordeaux- Hopital Saint Andre ( Site 4108)

Bordeaux, Gironde, 33075, France

Location

Institut Claudius Regaud ( Site 4105)

Toulouse, Haute-Garonne, 31059, France

Location

Centre Hospitalier Lyon Sud ( Site 4102)

Pierre-Bénite, Rhone, 69495, France

Location

A.P.H. Paris, Hopital Saint Louis ( Site 4107)

Paris, 75010, France

Location

Gustave Roussy ( Site 4101)

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

Location

HaEmek Medical Center ( Site 4703)

Afula, 1834111, Israel

Location

Rambam Health Care Campus-Oncology ( Site 4704)

Haifa, 3109601, Israel

Location

Hadassah Ein Karem Jerusalem ( Site 4702)

Jerusalem, 9112001, Israel

Location

Rabin Medical Center-Oncology ( Site 4705)

Petah Tikva, 4941492, Israel

Location

Chaim Sheba Medical Center ( Site 4701)

Ramat Gan, 5265601, Israel

Location

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 4399)

Milan, 20133, Italy

Location

Istituto Europeo di Oncologia ( Site 4301)

Milan, 20141, Italy

Location

Istituto Nazionale Tumori Fondazione Pascale ( Site 4302)

Napoli, 80131, Italy

Location

Istituto Oncologico Veneto IRCCS ( Site 4355)

Padua, 35128, Italy

Location

Policlinico Le Scotte - A.O. Senese ( Site 4377)

Siena, 53100, Italy

Location

CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE ( Site 4865)

Port Elizabeth, Eastern Cape, 6055, South Africa

Location

LIFE GROENKLOOF-Mary Potter Cancer Centre ( Site 4861)

Pretoria, Gauteng, 0181, South Africa

Location

Sandton Oncology Medical Group (Pty) Ltd-Research ( Site 4863)

Sandton, Gauteng, 2196, South Africa

Location

Cape Town Oncology Trials ( Site 4864)

Cape Town, Western Cape, 7570, South Africa

Location

HOSPITAL CLÍNIC DE BARCELONA-ICHMO- Clinic Institut of Haematological and Oncological diseases ( Site 4801)

Barcelona, Catalonia, 08036, Spain

Location

Hospital Universitario Ramón y Cajal ( Site 4802)

Madrid, Madrid, Comunidad de, 28034, Spain

Location

Hôpitaux Universitaires de Genève (HUG)-Oncology ( Site 4603)

Geneva, Canton of Geneva, 1211, Switzerland

Location

CHUV Centre Hospitalier Universitaire Vaudois ( Site 4602)

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Universitaetsspital Zuerich ( Site 4601)

Zurich, 8058, Switzerland

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Melanoma; Parkinson Disease 4, Autosomal Dominant Lewy Body

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: January 5, 2021
• First Posted: January 7, 2021
• Study Start: May 3, 2021
• Primary Completion: October 17, 2025
• Study Completion: October 17, 2025
• Last Updated: October 28, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

IL (5); IT (5); US (9); AU (2); FR (6); ZA (4); CH (3); ES (2)