Substudy 03B: A Study of Immune and Targeted Combination Therapies in Participants With Second Line Plus (2L+) Renal Cell Carcinoma (MK-3475-03B/KEYMAKER-U03)
Running, not enrolling · Phase 1/Phase 2
Conditions studied: Carcinoma, Renal Cell
In brief
Substudy 03B 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 03B is to evaluate the safety and efficacy of experimental combinations of investigational agents in participants with advanced second line plus (2L+) clear cell renal cell carcinoma (ccRCC). 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.
Key facts
- Study ID
- NCT04626518
- Run by
- Merck Sharp & Dohme LLC
- People needed
- 370
- Starts
- 2020-12-17
- Expected to finish
- 2026-08-21
- Last updated by the study team
- 2026-07-30
Who can join
Age: 18 and older. Sex: any. Healthy volunteers: not accepted.
You may qualify if…
- Has a histologically confirmed diagnosis of locally advanced/metastatic clear cell renal cell carcinoma (ccRCC)
- Has experienced disease progression on or after having received systemic treatment for locally advanced or metastatic RCC with a programmed cell death ligand 1 (PD-(L)1) checkpoint inhibitor (in sequence or in combination with a vascular endothelial growth factor. - tyrosine kinase inhibitor [VEGF-TKI]) where PD-(L)1 checkpoint inhibitor treatment progression is defined by meeting ALL of the following criteria: (a) has received ≥2 doses of an anti-PD-(L)1 monoclonal antibody (mAb) (b) has shown radiographic disease progression during or after an anti-PD-(L)1 mAb as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by investigator (c) disease progression has been documented within 12 weeks from the last dose of an anti-PD-(L)1 mAb
- Has experienced disease progression on or after having received systemic treatment for locally advanced or metastatic RCC with a VEGF-TKI (in sequence or in combination with a PD-[L]1 checkpoint inhibitor) where VEGF-TKI treatment progression is defined by meeting the following criterion: has shown radiographic disease progression during or after a treatment with a VEGF-TKI as defined by RECIST 1.1 by investigator.
- Is able to swallow oral medication
- Has adequate organ function
- Participants receiving bone resorptive therapy must have therapy initiated at least 2 weeks before randomization/allocation
- Has resolution of toxic effects of prior therapy to ≤Grade 1
- Has adequately controlled blood pressure (BP ≤150/90 mm Hg) with no change in hypertensive medications within 1 week before randomization/allocation
- Male participants are abstinent from heterosexual intercourse or agree to use contraception during treatment with and for at least 7 days after the last dose of lenvatinib and /or belzutifan; 7 days after lenvatinib and/or belzutifan is stopped, if the participant is only receiving pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab, MK-4830 or a combination of the aforementioned drugs, no contraception is needed
- Female participant is not pregnant or breastfeeding and is not a woman of childbearing potential (WOCBP) or is a WOCBP abstinent from heterosexual intercourse or using contraception during the intervention period and for at least 120 days after the last dose of pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab, MK-4830 or 30 days after the last dose of lenvatinib or belzutifan, whichever occurs last and must abstain from breastfeeding during the study intervention period and for at least 120 days after study intervention
You may not qualify if…
- Has urine protein ≥1 g/24 hours and has any of the following: (a) a pulse oximeter reading <92% at rest, or (b) requires intermittent supplemental oxygen, or (c) requires chronic supplemental oxygen (d) active hemoptysis within 3 weeks prior to the first dose of study intervention
- Has clinically significant cardiovascular disease within 12 months from the first dose of study intervention administration
- Has had major surgery within 3 weeks before first dose of study interventions
- Has a history of lung disease
- Has a history of inflammatory bowel disease
- Has preexisting gastrointestinal (GI) or non-GI fistula
- Has malabsorption due to prior GI surgery or disease
- Has previously received treatment with a combination of pembrolizumab plus lenvatinib
- Has received prior treatment with belzutifan
- Has received prior radiotherapy within 2 weeks of start of study intervention
- Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention; killed vaccines are allowed
- Has received more than 4 previous systemic anticancer treatment regimens
- Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
- Has known additional malignancy that is progressing or has required active treatment within the past 3 years
- Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has an active autoimmune disease that has required systemic treatment in the past 2 years; replacement therapy is not considered a form of systemic treatment and is allowed
- Has an active infection requiring systemic therapy
- Has a known history of human immunodeficiency virus (HIV) infection
- Has a known history of Hepatitis B
- Has had an allogenic tissue/solid organ transplant
Where it is running
- Yale-New Haven Hospital-Yale Cancer Center ( Site 3011) — New Haven, Connecticut, United States
- University of Chicago ( Site 3013) — Chicago, Illinois, United States
- University of Iowa ( Site 3012) — Iowa City, Iowa, United States
- Henry Ford Health System ( Site 3014) — Detroit, Michigan, United States
- Laura and Isaac Perlmutter Cancer Center ( Site 3016) — New York, New York, United States
- Memorial Sloan Kettering Cancer Center ( Site 3002) — New York, New York, United States
- Duke Cancer Institute ( Site 3015) — Durham, North Carolina, United States
- UPMC Cancer Center/Hillman Cancer Center ( Site 3017) — Pittsburgh, Pennsylvania, United States
- Vanderbilt University Medical Center ( Site 3004) — Nashville, Tennessee, United States
- UTSW Medical Center ( Site 3003) — Dallas, Texas, United States
- Blacktown Hospital ( Site 3601) — Blacktown, New South Wales, Australia
- St George Hospital ( Site 3602) — Kogarah, New South Wales, Australia
- Royal Brisbane and Women's Hospital ( Site 3603) — Herston, Queensland, Australia
- Austin Health ( Site 3600) — Melbourne, Victoria, Australia
- Princess Margaret Cancer Centre ( Site 3101) — Toronto, Ontario, Canada
- Jewish General Hospital ( Site 3100) — Montreal, Quebec, Canada
- James Lind Centro de Investigacion del Cancer ( Site 4108) — Temuco, Araucania, Chile
- CIDO SpA-Oncology ( Site 4106) — Temuco, Araucania, Chile
- FALP-UIDO ( Site 4100) — Santiago, Region M. de Santiago, Chile
- Bradfordhill-Clinical Area ( Site 4101) — Santiago, Region M. de Santiago, Chile
- ONCOCENTRO APYS-ACEREY ( Site 4103) — Viña del Mar, Valparaiso, Chile
- Institut De Cancerologie De Lorraine ( Site 3204) — Vandœuvre-lès-Nancy, Ain, France
- Institut de cancérologie Strasbourg Europe (ICANS) ( Site 3203) — Strasbourg, Alsace, France
- Institut Claudius Regaud ( Site 3200) — Toulouse, Haute-Garonne, France
- University of California at San Francisco ( Site 3008) — San Francisco, California, United States
Full record on ClinicalTrials.gov
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