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Looking for participantsPhase1/Phase2

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)

Sponsor: Merck Sharp & Dohme LLC

NCT ID: NCT07049926

View on ClinicalTrials.gov ↗

At a glance

What the study gets you
Access to the study treatment being tested
Type of study
Interventional (receives a drug or procedure)
Time in hospital
In-person visits at study sites — visit count not specified by the sponsor
Drug or intervention
Belzutifan (drug), Zanzalintinib (drug)
How long the study runs
Study runs about 75 months (dates as stated)
About the drug or intervention
Belzutifan — drug: Oral Tablet · Zanzalintinib — drug: Oral Tablet
Patient visit burden
Not specified by the sponsor
Type of study
Testing a treatment
Ages
18 Years to 120 Years
Who
All
Number of participants
140
Started
2025-07-20
Last checked
2026-09

Plain English Summary

What is this study?

  • • Testing a new treatment for renal cell carcinoma
  • • Phase1/Phase2 - 140 participants
  • • Substudy 03C is part of a larger research study that is testing experimental treatments for renal cell carcinoma (RCC)

Who can take part?

  • • Ages 18 Years to 120 Years
  • • Diagnosed with renal cell carcinoma

Where?

  • • Edinburgh - Western General Hospital ( Site 5402)
  • • Glasgow - The Beatson West of Scotland Cancer Centre ( Site 5405)
  • • London - St Bartholomew's Hospital ( Site 5401)
  • • Cardiff - Velindre Cancer Centre ( Site 5407)
  • • +1 more UK sites

This is a simplified summary. Always discuss with your doctor before making any decisions.

About This Trial

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

Renal Cell Carcinoma

How this trial compares with your answers

Answer 2 more questions to improve match

What we know so far

Condition· Matched your search
Age· Tell us your age for better matching
Gender· Tell us your sex for better matching

Still need:

  • • Tell us your age for better matching
  • • Tell us your sex for better matching

Preliminary match based on your answers. Full eligibility requires on-site assessment including medical history, physical exam, and lab tests. This does not guarantee enrolment.

Eligibility at a Glance

Key info

  • Age: 18 Years - 120 Years
  • Who can join: All genders

Treatment history

Treatments you must have had:

  • ✓ therapy initiated at least 2 weeks
  • ✓ active treatment within the past 3 years
  • ✓ systemic treatment in the past 2 years

What the study is looking for

  • ✓The main inclusion criteria include but are not limited to the following:
  • ✓Has a confirmed by a biopsy diagnosis of unresectable that has grown locally/that has spread kidney cell carcinoma (RCC) with...
  • ✓Has received no other prior treatment that goes through your whole body for treatment of advanced/that has spread clear cell kidney cell carcinoma...
  • ✓Has disease recurrence during after surgery anti- PD-(L)1 therapy or ≤24 months following the last dose of after surgery...
  • ✓Is able to swallow oral medication
See the full criteria
The main inclusion criteria include but are not limited to the following: * Has a histologically confirmed diagnosis of unresectable locally advanced/metastatic renal cell carcinoma (RCC) with clear cell component * 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 The main exclusion criteria include but are not limited to the following: * Has clinically significant hematuria, hematemesis, or hemoptysis of (\>2.5 mL) of red blood, or other history of significant bleeding * 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

Where Is This Study? (5 UK sites)

Western General Hospital ( Site 5402)

Edinburgh EH42XU, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator+441315371000

The Beatson West of Scotland Cancer Centre ( Site 5405)

Glasgow G12 0YN, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator+441413017064

St Bartholomew's Hospital ( Site 5401)

London EC1A7BE, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator+442072533411

Velindre Cancer Centre ( Site 5407)

Cardiff CF14 2TL, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator+442920615888

The Christie NHS Foundation Trust ( Site 5400)

Manchester M20 4BX, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator+441614463988

How to Get in Touch

Toll Free Number

Sponsor contact

CONTACT

1-888-577-8839 Trialsites@msd.com
Data sourced from ClinicalTrials.gov · Last verified: 2026-09