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)

NCT ID: NCT04700072

Last Updated: 2025-10-28

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

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

56 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-03

Study Completion Date

2025-10-17

Brief Summary

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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.

Detailed Description

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Conditions

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Melanoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Coformulation Pembrolizumab/Quavonlimab + Lenvatinib

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.

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

Pembrolizumab + Lenvatinib

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.

Group Type EXPERIMENTAL

Pembrolizumab

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

Interventions

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Pembrolizumab

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

Other Intervention Names

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

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* Has had major surgery \<3 weeks prior to first dose of study intervention
* Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention
* Has had an allogeneic tissue/solid organ transplant
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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The Angeles Clinic and Research Institute ( Site 4009)

Los Angeles, California, United States

Site Status

UCLA Hematology & Oncology ( Site 4004)

Los Angeles, California, United States

Site Status

Providence Saint John's Health Center ( Site 4010)

Santa Monica, California, United States

Site Status

University of Colorado, Anschutz Cancer Pavilion ( Site 4012)

Aurora, Colorado, United States

Site Status

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

Baltimore, Maryland, United States

Site Status

NYU Clinical Cancer Center ( Site 4002)

New York, New York, United States

Site Status

Duke Cancer Institute ( Site 4005)

Durham, North Carolina, United States

Site Status

Martha Morehouse Tower ( Site 4020)

Columbus, Ohio, United States

Site Status

Inova Schar Cancer Institute ( Site 4011)

Fairfax, Virginia, United States

Site Status

Calvary Mater Newcastle ( Site 4404)

Waratah, New South Wales, Australia

Site Status

Melanoma Institute Australia ( Site 4402)

Wollstonecraft, New South Wales, Australia

Site Status

Hopital La Timone ( Site 4103)

Marseille, Bouches-du-Rhone, France

Site Status

CHU de Bordeaux- Hopital Saint Andre ( Site 4108)

Bordeaux, Gironde, France

Site Status

Institut Claudius Regaud ( Site 4105)

Toulouse, Haute-Garonne, France

Site Status

Centre Hospitalier Lyon Sud ( Site 4102)

Pierre-Bénite, Rhone, France

Site Status

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

Paris, , France

Site Status

Gustave Roussy ( Site 4101)

Villejuif, Île-de-France Region, France

Site Status

HaEmek Medical Center ( Site 4703)

Afula, , Israel

Site Status

Rambam Health Care Campus-Oncology ( Site 4704)

Haifa, , Israel

Site Status

Hadassah Ein Karem Jerusalem ( Site 4702)

Jerusalem, , Israel

Site Status

Rabin Medical Center-Oncology ( Site 4705)

Petah Tikva, , Israel

Site Status

Chaim Sheba Medical Center ( Site 4701)

Ramat Gan, , Israel

Site Status

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

Milan, , Italy

Site Status

Istituto Europeo di Oncologia ( Site 4301)

Milan, , Italy

Site Status

Istituto Nazionale Tumori Fondazione Pascale ( Site 4302)

Napoli, , Italy

Site Status

Istituto Oncologico Veneto IRCCS ( Site 4355)

Padua, , Italy

Site Status

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

Siena, , Italy

Site Status

CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE ( Site 4865)

Port Elizabeth, Eastern Cape, South Africa

Site Status

LIFE GROENKLOOF-Mary Potter Cancer Centre ( Site 4861)

Pretoria, Gauteng, South Africa

Site Status

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

Sandton, Gauteng, South Africa

Site Status

Cape Town Oncology Trials ( Site 4864)

Cape Town, Western Cape, South Africa

Site Status

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

Barcelona, Catalonia, Spain

Site Status

Hospital Universitario Ramón y Cajal ( Site 4802)

Madrid, Madrid, Comunidad de, Spain

Site Status

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

Geneva, Canton of Geneva, Switzerland

Site Status

CHUV Centre Hospitalier Universitaire Vaudois ( Site 4602)

Lausanne, Canton of Vaud, Switzerland

Site Status

Universitaetsspital Zuerich ( Site 4601)

Zurich, , Switzerland

Site Status

Countries

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United States Australia France Israel Italy South Africa Spain Switzerland

Related Links

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Other Identifiers

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MK-3475-02D

Identifier Type: OTHER

Identifier Source: secondary_id

KEYMAKER-U02

Identifier Type: OTHER

Identifier Source: secondary_id

2023-506315-17-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1293-5704

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-003742-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

3475-02D

Identifier Type: -

Identifier Source: org_study_id

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