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Substudy 03C: Combination Therapies for Renal Cell Carcinoma

This study, called Substudy 03C, is part of a larger research effort to find new treatments for renal cell carcinoma (RCC), a type of kidney cancer. It's looking at combining two experimental drugs, Belzutifan and Zanzalintinib, given as oral tablets. You might be able to join if you have clear cell renal cell carcinoma that has come back or progressed during or after previous anti-PD-(L)1 therapy. The main goals are to understand how safe the drug combination is and how well it works. The study is currently unclear on its recruitment status and plans to enroll about 140 participants.

Study design
This is an interventional study with two phases: a safety lead-in phase and an efficacy phase. It is part of a larger umbrella study (U03).
What's involved
Not specified in the trial record.
Compensation
Not stated in the trial record.
Follow-up
Participants will be followed for safety events for up to approximately 74 months.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT07049926

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)

Recruiting
PHASE1Ages 18+InterventionalTreatment
Merck Sharp & Dohme LLC
~140 participants
Updated 2026-07-16 on ClinicalTrials.gov
What's tested:BelzutifanZanzalintinib

At a glance

Recruiting sites
30 of 30 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Safety Lead In Phase: Number of participants who experience one or more dose-limiting toxicities (DLTs)
Measured over Up to approximately 21 days
+6 more outcomes measured

Conditions

Renal Cell Carcinoma

Explore related trials

Renal Cell Carcinoma

Where it's being run

30 sites across 21 states
Israel4
New York3
South Korea3
Region M. de Santiago2
United Kingdom2
California1
North Carolina1
Pennsylvania1

Study leadership

  • Medical Director · STUDY_DIRECTOR · Merck Sharp & Dohme LLC

Who to contact

Toll Free Number
[email protected]
1-888-577-8839
Email the study team

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Do you actually qualify for this trial?

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Eligibility criteria

Inclusion

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

Exclusion

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

What this trial measures

  • Safety Lead In Phase: Number of participants who experience one or more dose-limiting toxicities (DLTs)Up to approximately 21 days

    DLTs are defined as any of a pre-specified list of toxicities if assessed by the investigator to be possibly, probably, or definitely related to study treatment administration, excluding toxicities clearly not related to the drug, such as disease progression, environmental factors, unrelated trauma, etc.

  • Safety Lead In Phase: Number of participants who experience one or more adverse events (AEs)Up to approximately 74 months

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

  • Safety Lead In Phase: Number of participants who discontinue study treatment due to an AEUp to approximately 74 months

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

  • Efficacy Phase: Number of participants who experience one or more DLTsUp to approximately 21 days

    DLTs are defined as any of a pre-specified list of toxicities if assessed by the investigator to be possibly, probably, or definitely related to study treatment administration, excluding toxicities clearly not related to the drug, such as disease progression, environmental factors, unrelated trauma, etc.

  • Efficacy Phase: Number of participants who experience one or more AEsUp to approximately 74 months

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

  • Efficacy Phase: Number of participants who discontinue study treatment due to an AEUp to approximately 74 months

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

  • Efficacy Phase: Objective Response Rate (ORR)Up to approximately 74 months

    ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.