Substudy 03A: A Study of Immune and Targeted Combination Therapies in Participants With First Line (1L) Renal Cell Carcinoma (MK-3475-03A)

Running, not enrolling · Phase 1/Phase 2

Conditions studied: Carcinoma, Renal Cell

In brief

Substudy 03A 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 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.

Key facts

Study ID

NCT04626479

Run by

Merck Sharp & Dohme LLC

People needed

400

Starts

2020-12-16

Expected to finish

2026-08-21

Last updated by the study team

2026-07-30

Who can join

Age: 18 and older, up to 120. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Has a histologically confirmed diagnosis of locally advanced/metastatic ccRCC
• 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

You may not qualify if…

• Has urine protein ≥1 g/24 hours and has any of the following: (a) a pulse oximeter reading <92% at rest, or (b) requires intermittent supplemental oxygen, or (c) requires chronic supplemental oxygen (d) active hemoptysis within 3 weeks prior to the first dose of study intervention
• 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

Where it is running

• 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
• Blacktown Hospital ( 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
• James Lind Centro de Investigacion del Cancer ( Site 2108) — Temuco, Araucania, Chile
• CIDO SpA-Oncology ( Site 2106) — Temuco, Araucania, Chile
• 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
• ONCOCENTRO APYS-ACEREY ( Site 2103) — Viña del Mar, Valparaiso, 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
• Instituto Médico de Alta Tecnologia S.A.S ( Site 1904) — Montería, Departamento de Córdoba, Colombia
• University of California at San Francisco ( Site 1008) — San Francisco, California, United States

Full record on ClinicalTrials.gov

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