RecruitingPhase 1Phase 2NCT07049926

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)

A Phase 1b/2 Study of Immune and Targeted Combination Therapies in Participants With RCC (KEYMAKER-U03): Substudy 03C in Participants With Recurrent Disease During or After Anti-PD-(L)1 Adjuvant Therapy

Sponsor

Merck Sharp & Dohme LLC

Enrollment

140 participants

Start Date

Jul 20, 2025

Study Type

INTERVENTIONAL

Conditions

Renal Cell Carcinoma

Summary

Substudy 03C is part of a larger research study that is testing experimental treatments for renal cell carcinoma (RCC). The larger study is the umbrella study (U03). 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

Eligibility

Min Age: 18 YearsMax Age: 120 Years

Plain Language Summary

Simplified for easier understanding

This trial tests combination treatment options for people with advanced kidney cancer (renal cell carcinoma) whose cancer came back during or after immunotherapy treatment (anti-PD-L1 therapy). It is part of a larger study platform testing multiple combinations. **You may be eligible if:** - You have been diagnosed with advanced or metastatic kidney cancer with a clear cell component - Your cancer returned during or within 24 months after completing immunotherapy in the adjuvant (post-surgery) setting - You have not received any other systemic treatment for advanced kidney cancer - You can swallow oral medications - You have adequate organ function and reasonably controlled blood pressure - You can provide a tumor tissue sample **You may NOT be eligible if:** - You have active brain metastases - You had a serious heart problem (e.g., heart attack, stroke) within the past 12 months - You have active autoimmune disease requiring treatment - You have serious bleeding, active infections, or recent major surgery - You have significant liver, kidney, or lung problems - You are on blood thinners that cannot be stopped - You have had a live vaccine within 30 days Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGBelzutifan

Oral Tablet

DRUGZanzalintinib

Oral Tablet

Locations(27)

UCSF Medical Center at Mission Bay ( Site 5008)

San Francisco, California, United States

Perlmutter Cancer Center at NYU Langone Hospital - Long Island ( Site 5026)

Mineola, New York, United States

Laura and Isaac Perlmutter Cancer Center ( Site 5016)

New York, New York, 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

UPMC Cancer Center/Hillman Cancer Center ( Site 5017)

Pittsburgh, Pennsylvania, United States

Centro de Estudios Clínicos SAGA ( Site 6110)

Santiago, Region M. de Santiago, Chile

Bradfordhill ( Site 6101)

Santiago, Region M. de Santiago, Chile

C.H.U. de Strasbourg Hopital de Hautepierre ( Site 5203)

Strasbourg, Bas-Rhin, France

Institut Claudius Regaud ( Site 5200)

Toulouse, Haute-Garonne, France

Centre Eugene Marquis ( Site 5205)

Rennes, Ille-et-Vilaine, France

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

Western General Hospital ( Site 5402)

Edinburgh, Edinburgh, City of, United Kingdom

St Bartholomew's Hospital ( Site 5401)

London, London, City of, United Kingdom

The Christie NHS Foundation Trust ( Site 5400)

Manchester, United Kingdom

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