Actively Recruiting
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)
Led by Merck Sharp & Dohme LLC · Updated on 2026-05-12
140
Participants Needed
28
Research Sites
327 weeks
Total Duration
On this page
Sponsors
M
Merck Sharp & Dohme LLC
Lead Sponsor
E
Exelixis
Collaborating Sponsor
AI-Summary
What this Trial Is About
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
CONDITIONS
Official Title
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)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically confirmed unresectable locally advanced or metastatic renal cell carcinoma with a clear cell component
- No prior systemic therapy for advanced or metastatic clear cell renal cell carcinoma except adjuvant PD-(L)1 therapy
- Disease recurrence during adjuvant anti-PD-(L)1 therapy or within 24 months after last dose
- Ability to swallow oral medication
- Submission of archival tumor tissue or new biopsy from a non-irradiated tumor lesion
- If receiving bone resorptive therapy, treatment started at least 2 weeks before randomization
- Adequately controlled blood pressure (≤140/90 mm Hg) without medication changes in the week before randomization
- Adequate organ function
You will not qualify if you...
- Clinically significant bleeding including hematuria, hematemesis, or hemoptysis >2.5 mL or history of significant bleeding
- Significant cardiovascular disease within 12 months before first study dose
- Deep vein thrombosis within 3 months before randomization unless stable, asymptomatic, and treated for at least 4 weeks
- History of idiopathic pulmonary fibrosis, organizing pneumonia, or active pneumonitis
- Serious wound, ulcer, or bone fracture or major surgery within 8 weeks before first study dose
- Symptomatic pleural effusion, ascites, or pericardial fluid requiring drainage within 4 weeks before randomization
- Gastrointestinal disorders with high risk of perforation or fistula
- Malabsorption from prior GI surgery or disease
- Moderate to severe liver impairment
- Use of colony-stimulating factors within 28 days before randomization
- Prior radiotherapy within 2 weeks before study start or radiation-related toxicities requiring corticosteroids
- Use of strong CYP3A4 inhibitors that cannot be stopped during study
- Live or live attenuated vaccine within 30 days before first study dose
- Current use of anticoagulants or platelet inhibitors that cannot be stopped during study
- Previous participation in any MK-3475-U03 substudy
- Active progressing malignancy requiring treatment in past 3 years
- Known active central nervous system metastases or carcinomatous meningitis
- Radiographic evidence of major blood vessel invasion or intratumoral cavitation
- Active autoimmune disease requiring systemic treatment in past 2 years
- Active infection needing systemic therapy
- History of HIV infection
- Hepatitis B or C virus infection
AI-Screening
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Trial Site Locations
Total: 28 locations
1
UCSF Medical Center at Mission Bay ( Site 5008)
San Francisco, California, United States, 94158
Actively Recruiting
2
Perlmutter Cancer Center at NYU Langone Hospital - Long Island ( Site 5026)
Mineola, New York, United States, 11501
Actively Recruiting
3
Laura and Isaac Perlmutter Cancer Center ( Site 5016)
New York, New York, United States, 10016
Actively Recruiting
4
Memorial Sloan Kettering Cancer Center ( Site 5002)
New York, New York, United States, 10065
Actively Recruiting
5
Duke Cancer Institute ( Site 5015)
Durham, North Carolina, United States, 27710
Actively Recruiting
6
UPMC Cancer Center/Hillman Cancer Center ( Site 5017)
Pittsburgh, Pennsylvania, United States, 15232
Actively Recruiting
7
Vanderbilt University Medical Center ( Site 5004)
Nashville, Tennessee, United States, 37232
Actively Recruiting
8
Centro de Estudios Clínicos SAGA ( Site 6110)
Santiago, Region M. de Santiago, Chile, 7500653
Actively Recruiting
9
Bradfordhill ( Site 6101)
Santiago, Region M. de Santiago, Chile, 8420383
Actively Recruiting
10
C.H.U. de Strasbourg Hopital de Hautepierre ( Site 5203)
Strasbourg, Bas-Rhin, France, 67098
Actively Recruiting
11
Institut Claudius Regaud ( Site 5200)
Toulouse, Haute-Garonne, France, 31059
Actively Recruiting
12
Centre Eugene Marquis ( Site 5205)
Rennes, Ille-et-Vilaine, France, 35042
Actively Recruiting
13
Institut De Cancerologie De Lorraine ( Site 5204)
Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France, 54513
Actively Recruiting
14
Gustave Roussy ( Site 5202)
Villejuif, Île-de-France Region, France, 94805
Actively Recruiting
15
Rambam Health Care Campus ( Site 5500)
Haifa, Israel, 3109601
Actively Recruiting
16
Rabin Medical Center ( Site 5502)
Petah Tikva, Israel, 4941492
Actively Recruiting
17
Sheba Medical Center ( Site 5501)
Ramat Gan, Israel, 5265601
Actively Recruiting
18
Sourasky Medical Center ( Site 5503)
Tel Aviv, Israel, 6423906
Actively Recruiting
19
Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 6201)
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland, 85-796
Actively Recruiting
20
Uniwersyteckie Centrum Kliniczne ( Site 6202)
Gdansk, Pomeranian Voivodeship, Poland, 80-214
Actively Recruiting
21
Severance Hospital ( Site 5802)
Seoul, South Korea, 03722
Actively Recruiting
22
Asan Medical Center ( Site 5800)
Seoul, South Korea, 05505
Actively Recruiting
23
Samsung Medical Center ( Site 5801)
Seoul, South Korea, 06351
Actively Recruiting
24
Hospital Universitario Ramon y Cajal ( Site 5301)
Madrid, Madrid, Comunidad de, Spain, 28034
Actively Recruiting
25
Hospital Universitari Vall d'Hebron ( Site 5300)
Barcelona, Spain, 08035
Actively Recruiting
26
Western General Hospital ( Site 5402)
Edinburgh, Edinburgh, City of, United Kingdom, EH42XU
Actively Recruiting
27
St Bartholomew's Hospital ( Site 5401)
London, London, City of, United Kingdom, EC1A7BE
Actively Recruiting
28
The Christie NHS Foundation Trust ( Site 5400)
Manchester, United Kingdom, M20 4BX
Actively Recruiting
Research Team
T
Toll Free Number
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
SINGLE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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