Substudy 03C: A Study of Combination Therapies in Participants With Renal Cell Carcinoma With Recurrent Disease During or After Anti-PD-(L)1 Therapy (MK-3475-03C/KEYMAKER-U03)
NCT ID: NCT07049926
Last Updated: 2025-11-10
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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RECRUITING
PHASE1/PHASE2
140 participants
INTERVENTIONAL
2025-07-20
2031-10-26
Brief Summary
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The goal of substudy 03C is to evaluate the safety and efficacy of experimental combinations of investigational agents in participants with clear cell renal cell carcinoma (ccRCC) who have recurrent disease during or after anti-programmed cell death 1/programmed cell death ligand 1 (PD-\[L\]1) adjuvant therapy.
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
Detailed Description
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Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
SINGLE
Study Groups
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Zanzalintinib at Dose Level 1 or 2 + Belzutifan
Participants will be allocated to receive zanzalintinib at dose level 1 or 2 + belzutifan daily until progressive disease or discontinuation
Belzutifan
Oral Tablet
Zanzalintinib
Oral Tablet
Belzutifan
Participants will receive belzutifan daily until progressive disease or discontinuation
Belzutifan
Oral Tablet
Interventions
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Belzutifan
Oral Tablet
Zanzalintinib
Oral Tablet
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Has received no other prior systemic therapy for treatment of advanced/metastatic clear cell renal cell carcinoma (ccRCC) except for adjuvant programmed cell death ligand 1 (PD-(L)1) therapy
* Has disease recurrence during adjuvant anti- PD-(L)1 therapy or ≤24 months following the last dose of adjuvant anti-PD-(L)1 therapy
* Is able to swallow oral medication
* Submits an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
* Participants receiving bone resorptive therapy (must have therapy initiated at least 2 weeks before allocation/randomization)
* Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤140/90 mm Hg with no change in antihypertensive medications within 1 week before allocation/randomization
* Has adequate organ function
Exclusion Criteria
* Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
* Has deep vein thrombosis within 3 months before allocation/randomization unless stable, asymptomatic, and treated with therapeutic anticoagulation for at least 4 weeks before allocation/randomization
* Has history of idiopathic pulmonary fibrosis, organizing pneumonia, or evidence of active pneumonitis
* Has serious wound, ulcer or bone fracture or has had major surgery within 8 weeks before first dose of study intervention
* Has symptomatic pleural effusion (for example cough, dyspnea, pleuritic chest pain), ascites, or pericardial fluid requiring drainage in the last 4 weeks before allocation/randomization
* Has gastrointestinal (GI) disorders, including those associated with a high risk of perforation or fistula formation
* Has malabsorption due to prior GI surgery or GI disease
* Has moderate to severe hepatic impairment
* Has received colony-stimulating factors within 28 days prior to intervention allocation/randomization
* Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
* Is currently receiving strong inhibitors of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of the study
* Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention
* Is currently receiving anticoagulants or platelet inhibitors that cannot be discontinued for the duration of the study
* Have been previously allocated/randomized to study intervention in any sub study of protocol MK-3475-U03
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
* Has active autoimmune disease that has required systemic treatment in the past 2 years
* Has an active infection requiring systemic therapy
* Has history of human immunodeficiency virus (HIV) infection
* Has hepatitis B or hepatitis C virus infection
18 Years
120 Years
ALL
No
Sponsors
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Exelixis
INDUSTRY
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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UCSF Medical Center at Mission Bay ( Site 5008)
San Francisco, California, United States
Memorial Sloan Kettering Cancer Center ( Site 5002)
New York, New York, United States
Duke Cancer Institute ( Site 5015)
Durham, North Carolina, United States
Institut De Cancerologie De Lorraine ( Site 5204)
Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France
Gustave Roussy ( Site 5202)
Villejuif, Île-de-France Region, France
Rambam Health Care Campus ( Site 5500)
Haifa, , Israel
Rabin Medical Center ( Site 5502)
Petah Tikva, , Israel
Sheba Medical Center ( Site 5501)
Ramat Gan, , Israel
Sourasky Medical Center ( Site 5503)
Tel Aviv, , Israel
Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 6201)
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland
Uniwersyteckie Centrum Kliniczne ( Site 6202)
Gdansk, Pomeranian Voivodeship, Poland
Severance Hospital ( Site 5802)
Seoul, , South Korea
Asan Medical Center ( Site 5800)
Seoul, , South Korea
Samsung Medical Center ( Site 5801)
Seoul, , South Korea
Hospital Universitario Ramon y Cajal ( Site 5301)
Madrid, Madrid, Comunidad de, Spain
Hospital Universitari Vall d'Hebron ( Site 5300)
Barcelona, , Spain
St Bartholomew's Hospital ( Site 5401)
London, London, City of, United Kingdom
The Christie NHS Foundation Trust ( Site 5400)
Manchester, , United Kingdom
Countries
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Central Contacts
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Facility Contacts
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Study Coordinator
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Study Coordinator
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Study Coordinator
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Study Coordinator
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Study Coordinator
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Study Coordinator
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Study Coordinator
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Study Coordinator
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Study Coordinator
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Study Coordinator
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Study Coordinator
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Study Coordinator
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Related Links
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Merck Clinical Trials Information
Other Identifiers
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MK-3475-03C
Identifier Type: OTHER
Identifier Source: secondary_id
2024-516437-12-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
U1111-1310-6076
Identifier Type: REGISTRY
Identifier Source: secondary_id
KEYMAKER-U03
Identifier Type: OTHER
Identifier Source: secondary_id
3475-03C
Identifier Type: -
Identifier Source: org_study_id