Substudy 02A: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents in Participants With Programmed Cell-death 1 (PD-1) Refractory Melanoma (MK-3475-02A/KEYMAKER-U02)
NCT ID: NCT04305041
Last Updated: 2025-08-29
Study Results
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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COMPLETED
PHASE1/PHASE2
100 participants
INTERVENTIONAL
2020-06-26
2025-08-25
Brief Summary
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The goal of substudy 02A is to evaluate the safety and efficacy of investigational treatment arms in participants with PD-1 refractory melanoma to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available.
As of Amendment 4 (effective date: 05JAN2022), a third arm has been opened to participant enrollment, treatment with pembrolizumab and all-trans retinoic acid (ATRA). Enrollment into the first two arms, treatment with pembrolizumab + quavonlimab+ vibostolimab and treatment with pembrolizumab + quavonlimab + lenvatinib has been completed per protocol as of September 2021.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Pembrolizumab + Quavonlimab + Vibostolimab
Participants will receive pembrolizumab intravenously (IV) plus quavonlimab IV plus vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.
Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Quavonlimab
Administered via IV infusion at a specified dose on specified days
Vibostolimab
Administered via IV infusion at a specified dose on specified days
Pembrolizumab + Quavonlimab + Lenvatinib
Participants will receive pembrolizumab IV plus quavonlimab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Quavonlimab
Administered via IV infusion at a specified dose on specified days
Lenvatinib
Administered via oral capsules at a specified dose on specified days
Pembrolizumab + all-trans retinoic acid (ATRA)
Participants will receive pembrolizumab IV plus ATRA orally at specified doses on specified days for a total treatment duration of up to approximately 2 years
ATRA
Administered via oral capsules at a specified dose on specified days
Interventions
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Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Quavonlimab
Administered via IV infusion at a specified dose on specified days
Vibostolimab
Administered via IV infusion at a specified dose on specified days
Lenvatinib
Administered via oral capsules at a specified dose on specified days
ATRA
Administered via oral capsules at a specified dose on specified days
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Has unresectable Stage III or Stage IV melanoma, not amenable to local therapy
* Has progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other therapies
* Has imaging documenting progression per RECIST 1.1 and iRECIST after initiation of an anti-PD-1/L1 agent, or by RECIST 1.1 if progression occurred on adjuvant therapy or in the setting of rapid progression.
* Has not received more than 3 lines of therapy for their advanced melanoma
* Has provided a tumor biopsy
* Male participants who receive lenvatinib or ATRA are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 7 days after the last dose of lenvatinib or ATRA; for male participants who only receive pembrolizumab, quavonlimab, vibostolimab, or a combination, no contraception measures are needed
* Female participant 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, quavonlimab, vibostolimab or 30 days after the last dose of lenvatinib or ATRA, whichever occurs last
* Has adequate organ function
* Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia)
Exclusion Criteria
* 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 known hypersensitivity including previous clinically significant hypersensitivity reaction to treatment with another mAb
* 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 known history of hepatitis B
* 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 pre-existing Grade ≥3 gastrointestinal fistula or nongastrointestinal fistula
* Has radiographic evidence of encasement of invasion of 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
18 Years
120 Years
ALL
No
Sponsors
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Merck Sharp & Dohme LLC
INDUSTRY
Responsible Party
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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 1009)
Los Angeles, California, United States
UCLA Hematology & Oncology ( Site 1004)
Los Angeles, California, United States
Providence Saint John's Health Center ( Site 1010)
Santa Monica, California, United States
University of Colorado, Anschutz Cancer Pavilion ( Site 1012)
Aurora, Colorado, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 1022)
Baltimore, Maryland, United States
NYU Clinical Cancer Center ( Site 1002)
New York, New York, United States
Duke Cancer Institute ( Site 1005)
Durham, North Carolina, United States
Martha Morehouse Tower ( Site 1020)
Columbus, Ohio, United States
Oregon Health & Science University ( Site 1013)
Portland, Oregon, United States
University of Pennsylvania Abramson Cancer Center ( Site 1008)
Philadelphia, Pennsylvania, United States
West Cancer Center - East Campus ( Site 1014)
Germantown, Tennessee, United States
University of Texas MD Anderson Cancer Center ( Site 1006)
Houston, Texas, United States
Inova Schar Cancer Institute ( Site 1011)
Fairfax, Virginia, United States
Calvary Mater Newcastle-Medical Oncology ( Site 1404)
Waratah, New South Wales, Australia
Melanoma Institute Australia ( Site 1402)
Wollstonecraft, New South Wales, Australia
Tasman Oncology Research Pty Ltd ( Site 1403)
Southport, Queensland, Australia
Fiona Stanley Hospital ( Site 1401)
Murdoch, Western Australia, Australia
Hopital La Timone ( Site 1103)
Marseille, Bouches-du-Rhone, France
Hopital Saint Andre ( Site 1108)
Bordeaux, Gironde, France
Institut Claudius Regaud ( Site 1105)
Toulouse, Haute-Garonne, France
Centre Hospitalier Lyon Sud ( Site 1102)
Pierre-Bénite, Rhone, France
A.P.H. Paris, Hopital Saint Louis ( Site 1107)
Paris, , France
Gustave Roussy ( Site 1101)
Villejuif, Île-de-France Region, France
HaEmek Medical Center ( Site 1703)
Afula, , Israel
Rambam Health Care Campus-Oncology ( Site 1704)
Haifa, , Israel
Hadassah Ein Karem Jerusalem ( Site 1702)
Jerusalem, , Israel
Chaim Sheba Medical Center ( Site 1701)
Ramat Gan, , Israel
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 1399)
Milan, , Italy
Istituto Europeo di Oncologia ( Site 1301)
Milan, , Italy
Istituto Nazionale Tumori Fondazione Pascale ( Site 1302)
Napoli, , Italy
Istituto Oncologico Veneto IRCCS ( Site 1355)
Padua, , Italy
Policlinico Le Scotte - A.O. Senese ( Site 1377)
Siena, , Italy
CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE-Clinical Trials Unit ( Site 1865)
Port Elizabeth, Eastern Cape, South Africa
Hôpitaux Universitaires de Genève (HUG)-Oncology ( Site 1603)
Geneva, Canton of Geneva, Switzerland
CHUV Centre Hospitalier Universitaire Vaudois ( Site 1602)
Lausanne, Canton of Vaud, Switzerland
Universitaetsspital Zuerich ( Site 1601)
Zuerich Flughafen, Canton of Zurich, Switzerland
Countries
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Related Links
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Merck Clinical Trials Information
Plain Language Summary
Other Identifiers
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MK-3475-02A
Identifier Type: OTHER
Identifier Source: secondary_id
KEYMAKER-U02
Identifier Type: OTHER
Identifier Source: secondary_id
2023-506312-41-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
U1111-1293-5630
Identifier Type: REGISTRY
Identifier Source: secondary_id
2019-003956-35
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
3475-02A
Identifier Type: -
Identifier Source: org_study_id
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