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)
| NCT ID | NCT07049926 |
| Status | Recruiting |
| Phase | Phase 1, Phase 2 |
| Sponsor | Merck Sharp & Dohme LLC |
| Condition | Renal Cell Carcinoma |
| Study Type | INTERVENTIONAL |
| Enrollment | 140 participants |
| Start Date | 2025-07-20 |
| Primary Completion | 2031-10-26 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
Phase 1 is the earliest stage of human testing — safety and dosage are the primary focus. Visits are frequent and medical supervision is intensive. You will be among the first people to receive this treatment.
This trial targets 140 participants in total. It began in 2025-07-20 with a primary completion date of 2031-10-26.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
Brief 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 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
Contact & Investigator
Medical Director
STUDY DIRECTOR
Merck Sharp & Dohme LLC
Frequently Asked Questions
Who can join the NCT07049926 clinical trial?
This trial is open to participants of all sexes, aged 18 Years or older, up to 120 Years, studying Renal Cell Carcinoma. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT07049926 trial and what does that mean for participants?
Phase 1 trials are the first stage of human testing. The primary goal is to assess safety and determine appropriate dosage levels. Participants are closely monitored. These trials typically involve a small number of volunteers.
Is NCT07049926 currently recruiting?
Yes, NCT07049926 is actively recruiting participants. Contact the research team at Trialsites@msd.com for enrollment information.
Where is the NCT07049926 trial being conducted?
This trial is being conducted at San Francisco, United States, Mineola, United States, New York, United States, New York, United States and 11 additional locations.
Who is sponsoring the NCT07049926 clinical trial?
NCT07049926 is sponsored by Merck Sharp & Dohme LLC. The principal investigator is Medical Director at Merck Sharp & Dohme LLC. The trial plans to enroll 140 participants.