Substudy 03A: A Study of Immune and Targeted Combination Therapies in Participants With First Line (1L) Renal Cell Carcinoma (MK-3475-03A)
NCT ID: NCT04626479
Last Updated: 2025-02-17
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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ACTIVE_NOT_RECRUITING
PHASE1/PHASE2
400 participants
INTERVENTIONAL
2020-12-16
2026-05-31
Brief Summary
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The goal of substudy 03A is to evaluate the safety and efficacy of experimental combinations of investigational agents in participants with advanced first line (1L) clear cell renal cell carcinoma (ccRCC).
This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to demonstrate a tolerable safety profile for the combination of investigational agents. There will be no hypothesis testing in this study.
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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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Coformulation Pembrolizumab/Quavonlimab + Lenvatinib
Participants will receive pembrolizumab/quavonlimab (coformulation of pembrolizumab 400 mg and quavonlimab 25 mg) PLUS lenvatinib 20 mg. Pembrolizumab/quavonlimab will be administered intravenously (IV) once every 6 weeks (Q6W) for up to 17 administrations (up to \~2 years). Lenvatinib will be administered orally once-daily (QD) until progressive disease or discontinuation.
Lenvatinib
Administered via oral capsule at a dose of 20 mg QD
Pembrolizumab/Quavonlimab
Administered via IV infusion at a dose of 400 mg/25 mg Q6W
Coformulation Favezelimab/Pembrolizumab+ Lenvatinib
Participants will receive favezelimab/pembrolizumab (coformulation of favezelimab 800 mg and pembrolizumab 200 mg) PLUS lenvatinib 20 mg. Favezelimab/Pembrolizumab will be administered IV once every 3 weeks (Q3W) for up to 35 administrations (up to \~2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.
Favezelimab/Pembrolizumab
Administered via IV infusion at a dose of 800 mg/200 mg Q3W
Lenvatinib
Administered via oral capsule at a dose of 20 mg QD
Pembrolizumab + Belzutifan + Lenvatinib
Participants will receive pembrolizumab 400 mg PLUS belzutifan 120 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered IV Q6W for up to 17 administrations (up to \~2 years). Both belzutifan and lenvatinib will be administered orally QD until progressive disease or discontinuation.
Pembrolizumab
Administered via IV infusion at a dose of 400 mg Q6W
Belzutifan
Administered via oral tablet at a dose of 120 mg QD
Lenvatinib
Administered via oral capsule at a dose of 20 mg QD
Pembrolizumab + Lenvatinib
Participants will receive pembrolizumab 400 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered IV Q6W for up to 17 administrations (up to \~ 2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.
Pembrolizumab
Administered via IV infusion at a dose of 400 mg Q6W
Lenvatinib
Administered via oral capsule at a dose of 20 mg QD
Coformulation Vibostolimab/Pembrolizumab+Belzutifan
Participants will receive vibostolimab/pembrolizumab (coformulation of 200 mg vibostolimab and pembrolizumab 200 mg). Vibostolimab/pembrolizumab will be administered IV once every 3 weeks (Q3W) for up to 35 administrations (up to \~2 years). Belzutifan will be administered orally QD until progressive disease or discontinuation.
Belzutifan
Administered via oral tablet at a dose of 120 mg QD
Vibostolimab/Pembrolizumab
Administered via IV infusion at a dose of 200 mg/200 mg Q6W
Interventions
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Pembrolizumab
Administered via IV infusion at a dose of 400 mg Q6W
Favezelimab/Pembrolizumab
Administered via IV infusion at a dose of 800 mg/200 mg Q3W
Belzutifan
Administered via oral tablet at a dose of 120 mg QD
Lenvatinib
Administered via oral capsule at a dose of 20 mg QD
Pembrolizumab/Quavonlimab
Administered via IV infusion at a dose of 400 mg/25 mg Q6W
Vibostolimab/Pembrolizumab
Administered via IV infusion at a dose of 200 mg/200 mg Q6W
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Has received no prior systemic therapy for advanced RCC; prior neoadjuvant/adjuvant therapy for RCC is acceptable if completed ≥12 months before randomization/allocation.
* Is able to swallow oral medication
* Has adequate organ function
* Participants receiving bone resorptive therapy must have therapy initiated at least 2 weeks before randomization/allocation
* Has resolution of toxic effects of the most recent prior therapy to ≤Grade 1
* Has adequately controlled blood pressure (BP ≤150/90 mm Hg) with no change in hypertensive medications within 1 week before randomization/allocation
* Male participants are abstinent from heterosexual intercourse or agree to use contraception during treatment with and for at least 7 days after the last dose of lenvatinib and /or belzutifan; 7 days after lenvatinib and/or belzutifan is stopped, if the participant is only receiving pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab or a combination of the aforementioned drugs, no contraception is needed
* Female participants must not be pregnant and not be a woman of childbearing potential (WOCBP) or is a WOCBP abstinent from heterosexual intercourse or using contraception during the intervention period and for at least 120 days after the last dose of pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab for 30 days after the last dose of lenvatinib or belzutifan, whichever occurs last and must abstain from breastfeeding during the study intervention period and for at least 120 days after study intervention
Exclusion Criteria
* Has clinically significant cardiovascular disease within 12 months from the first dose of study intervention administration
* Has had major surgery within 3 weeks before first dose of study interventions
* Has a history of lung disease
* Has a history of inflammatory bowel disease
* Has preexisting gastrointestinal (GI) or non-GI fistula
* Has malabsorption due to prior GI surgery or disease
* Has received prior radiotherapy within 2 weeks of start of study intervention
* Has received a live or live attenuated vaccine within 30 days before the first dose of study drug; killed vaccines are allowed
* Has received more than 4 previous systemic anticancer treatment regimens
* Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has an active autoimmune disease that has required systemic treatment in the past 2 years; replacement therapy is not considered a form of systemic treatment and is allowed
* Has an active infection requiring systemic therapy
* Has a known history of human immunodeficiency virus (HIV) infection
* Has a known history of Hepatitis B
* Has had an allogenic tissue/solid organ transplant
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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University of California at San Francisco ( Site 1008)
San Francisco, California, United States
Yale-New Haven Hospital-Yale Cancer Center ( Site 1011)
New Haven, Connecticut, United States
University of Chicago ( Site 1013)
Chicago, Illinois, United States
University of Iowa ( Site 1012)
Iowa City, Iowa, United States
Henry Ford Health System ( Site 1014)
Detroit, Michigan, United States
Laura and Isaac Perlmutter Cancer Center ( Site 1016)
New York, New York, United States
Memorial Sloan Kettering Cancer Center ( Site 1002)
New York, New York, United States
Duke Cancer Institute ( Site 1015)
Durham, North Carolina, United States
UPMC Cancer Center/Hillman Cancer Center ( Site 1017)
Pittsburgh, Pennsylvania, United States
UTSW Medical Center ( Site 1003)
Dallas, Texas, United States
Western Sydney Local Health District ( Site 1601)
Blacktown, New South Wales, Australia
St George Hospital ( Site 1602)
Kogarah, New South Wales, Australia
Royal Brisbane and Women s Hospital ( Site 1603)
Herston, Queensland, Australia
Austin Health ( Site 1600)
Heidelberg, Victoria, Australia
Princess Margaret Cancer Centre ( Site 1101)
Toronto, Ontario, Canada
Jewish General Hospital ( Site 1100)
Montreal, Quebec, Canada
FALP-UIDO ( Site 2100)
Santiago, Region M. de Santiago, Chile
Oncovida ( Site 2107)
Santiago, Region M. de Santiago, Chile
Bradfordhill-Clinical Area ( Site 2101)
Santiago, Region M. de Santiago, Chile
James Lind Centro de Investigación del Cáncer ( Site 2108)
Temuco, Región de la Araucanía, Chile
CIDO SpA-Oncology ( Site 2106)
Temuco, Región de la Araucanía, Chile
ONCOCENTRO APYS-ACEREY ( Site 2103)
Viña del Mar, Región de Valparaíso, Chile
Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia-Center Investigator ( Site 1900)
Bogotá, Bogota D.C., Colombia
Sociedad De Oncologia Y Hematologia Del Cesar-Oncology ( Site 1905)
Valledupar, Cesar Department, Colombia
Oncomédica S.A.S ( Site 1904)
Montería, Departamento de Córdoba, Colombia
Fundación Valle del Lili ( Site 1901)
Cali, Valle del Cauca Department, Colombia
Institut De Cancerologie De Lorraine ( Site 1204)
Vandœuvre-lès-Nancy, Ain, France
Institut de cancérologie Strasbourg Europe (ICANS) ( Site 1203)
Strasbourg, Alsace, France
Institut Claudius Regaud ( Site 1200)
Toulouse, Haute-Garonne, France
Gustave Roussy ( Site 1202)
Villejuif, Val-de-Marne, France
Országos Onkológiai Intézet-Urogenitális Tumorok és Klinikai Farmakológiai Osztály ( Site 2301)
Budapest, Pest County, Hungary
Rambam MC ( Site 1500)
Haifa, , Israel
Hadassah Medical Center-Oncology ( Site 1504)
Jerusalem, , Israel
Rabin Medical Center ( Site 1502)
Petah Tikva, , Israel
Sheba Medical Center - Oncology Division ( Site 1501)
Ramat Gan, , Israel
Sourasky Medical Center ( Site 1503)
Tel Aviv, , Israel
Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)-medical oncology ( Site 2402)
Amsterdam, North Holland, Netherlands
Erasmus Medisch Centrum ( Site 2401)
Rotterdam, South Holland, Netherlands
Auckland City Hospital ( Site 1700)
Auckland, , New Zealand
Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 2201)
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 2200
Warsaw, Masovian Voivodeship, Poland
Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 2202)
Gdansk, Pomeranian Voivodeship, Poland
Asan Medical Center ( Site 1800)
Songpagu, Seoul, South Korea
Severance Hospital ( Site 1802)
Seoul, , South Korea
Samsung Medical Center ( Site 1801)
Seoul, , South Korea
Hospital Universitari Vall d Hebron ( Site 1300)
Barcelona, Catalonia, Spain
Hospital Universitario Ramon y Cajal ( Site 1301)
Madrid, , Spain
Southampton General Hospital ( Site 1403)
Southampton, England, United Kingdom
The Beatson West of Scotland Cancer Centre ( Site 1405)
Glasgow, Glasgow City, United Kingdom
Royal Preston Hospital ( Site 1406)
Preston, Lancashire, United Kingdom
Leicester Royal Infirmary ( Site 1408)
Leicester, Leicestershire, United Kingdom
Barts Health NHS Trust ( Site 1401)
London, London, City of, United Kingdom
Western General Hospital ( Site 1402)
Edinburgh, Midlothian, United Kingdom
Velindre Cancer Centre Hospital ( Site 1407)
Cardiff, Wales, United Kingdom
The Christie NHS Foundation Trust ( Site 1400)
Manchester, , United Kingdom
Countries
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Related Links
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Merck Oncology Clinical Trials Information
Plain Language Summary
Other Identifiers
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MK-3475-03A
Identifier Type: OTHER
Identifier Source: secondary_id
2023-506838-68-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
2019-003609-84
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
3475-03A
Identifier Type: -
Identifier Source: org_study_id
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