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NCT07049926PHASE1, PHASE2RECRUITING

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 + Exelixis

No open prediction endpoints

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Key Facts

Study type
INTERVENTIONAL
Conditions
Renal Cell Carcinoma
Interventions
Belzutifan, Zanzalintinib
Enrollment
140 participants
Primary completion
Oct 2031
Study completion
Oct 2031
First posted
Jul 2025
Last updated
May 2026

Primary Endpoints (CT.gov)

Safety Lead In Phase: Number of participants who experience one or more dose-limiting toxicities (DLTs)

Time frame: Up to approximately 21 days

Safety Lead In Phase: Number of participants who experience one or more adverse events (AEs)

Time frame: Up to approximately 74 months

Safety Lead In Phase: Number of participants who discontinue study treatment due to an AE

Time frame: Up to approximately 74 months

Efficacy Phase: Number of participants who experience one or more DLTs

Time frame: Up to approximately 21 days

Secondary Endpoints

Efficacy Phase: Duration of response (DOR)

Efficacy Phase: Progression-free survival (PFS)

Efficacy Phase: Overall survival (OS)

Eligibility 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 medica

Read full criteria on CT.gov →

✦ Analyst Commentary

Expert commentary on why this trial matters and what to watch for.

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Source

Open on ClinicalTrials.gov