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Clinical Trials in the UK / NCT04736706
Active, not recruiting Phase 3

A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012)

NCT04736706 · tracked via the Priya Life Science UK tracker
Sponsor
Merck Sharp & Dohme LLC
Phase
Phase 3
Started
2021-04-14
Last updated
2026-08-14

Condition(s) studied

Carcinoma, Renal Cell

Investigational drug(s) / intervention(s)

PembrolizumabBelzutifanPembrolizumab/QuavonlimabLenvatinib

Pembrolizumab: Pembrolizumab 400 mg administered Q6W via IV infusion

Belzutifan: Belzutifan 120 mg administered QD via oral tablet

Pembrolizumab/Quavonlimab: Pembrolizumab/quavonlimab is a co-formulated product composed of pembrolizumab 400 mg in combination with quavonlimab 25 mg, administered Q6W via IV infusion

Lenvatinib: Lenvatinib 20 mg administered QD via oral capsule

Study summary

The goal of this study is to evaluate the efficacy and safety of pembrolizumab plus belzutifan plus lenvatinib or pembrolizumab/quavonlimab plus lenvatinib versus pembrolizumab plus lenvatinib as first-line treatment in participants with advanced clear cell renal cell carcinoma (ccRCC).

The primary hypotheses are (1) pembrolizumab plus belzutifan plus lenvatinib is superior to pembrolizumab plus lenvatinib with respect to progression-free survival (PFS) and overall survival (OS), in advanced ccRCC participants; and (2) pembrolizumab/quavonlimab plus lenvatinib is superior to pembrolizumab plus lenvatinib with respect to PFS and OS, in advanced ccRCC participants.

Eligibility

Sex
ALL
Min age
18 Years
Max age
Healthy volunteers
No
Inclusion Criteria: * Has histologically confirmed diagnosis of RCC with clear cell component. * Has received no prior systemic therapy for advanced ccRCC * Male participants are abstinent from heterosexual intercourse or agree to use contraception during and for at least 7 days after last dose of study intervention with belzutifan and lenvatinib. * Female participants are not pregnant or breastfeeding and are either not a woman of child-bearing potential (WOCBP) or use a contraceptive method that is highly effective or are abstinent from heterosexual intercourse during the intervention period and for at least 120 days after pembrolizumab or pembrolizumab/quavonlimab or for at least 30 days after last dose of lenvatinib or belzutifan, whichever occurs last * Has adequately controlled blood pressure with or without antihypertensive medications * Has adequate organ function. * Participants receiving bone resorptive therapy must have therapy initiated at least 2 weeks prior to randomization/allocation Exclusion Criteria: * Has a known additional malignancy that is progressing or has required active treatment within the past 3 years * Has had major surgery, other than nephrectomy within 4 weeks prior to randomization * Has known central nervous system (CNS) metastases and/or carcinomatous meningitis * Has received prior radiotherapy within 2 weeks prior to first dose of study intervention * Has hypoxia or requires intermittent supplemental oxygen or requires chronic supplemental oxygen * Has clinically significant cardiac disease within 12 months from first dose of study intervention * Has a history of interstitial lung disease * Has symptomatic pleural effusion; a participant who is clinically stable following treatment of this condition is eligible * Has preexisting gastrointestinal or non-gastrointestinal fistula * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment * Has a known psychiatric or substance abuse disorder that would interfere with requirements of the study * Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug; killed vaccines are allowed * Has an active autoimmune disease that has required systemic treatment in the past 2 years * Has a history of noninfectious pneumonitis that required steroids or has current pneumonitis * 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 radiographic evidence of intratumoral cavitation, encasement or invasion of a major blood vessel * Has clinically significant history of bleeding within 3 months prior to randomization * Has had an allogenic tissue/solid organ transplant

Primary outcome measure(s)

Trial sites (262)

FacilityCityRegionStatus
The University of Alabama at Birmingham ( Site 0010) Birmingham Alabama
UC San Diego ( Site 0050) La Jolla California
Cedars Sinai Medical Center ( Site 0027) Los Angeles California
University of California Irvine ( Site 0029) Orange California
UCLA Hematology Oncology Santa Monica ( Site 0048) Santa Monica California
Hartford Hospital ( Site 0024) Hartford Connecticut
Advent Health Hematology & Oncology ( Site 0003) Orlando Florida
University Cancer & Blood Center, LLC ( Site 0057) Athens Georgia
Emory University Winship Cancer Institute ( Site 0012) Atlanta Georgia
Rush University Medical Center ( Site 0040) Chicago Illinois
Parkview Cancer Institute ( Site 0088) Fort Wayne Indiana
Norton Cancer Institute - St. Matthews ( Site 0065) Louisville Kentucky
Ochsner Medical Center ( Site 0049) New Orleans Louisiana
New England Cancer Specialists ( Site 0082) Scarborough Maine
Massachusetts General Hospital ( Site 0094) Boston Massachusetts
Beth Israel Deaconess Medical Center ( Site 0089) Boston Massachusetts
Dana Farber Cancer Institute ( Site 0093) Boston Massachusetts
Lahey Hospital & Medical Center ( Site 0090) Burlington Massachusetts
Henry Ford Hospital ( Site 0038) Detroit Michigan
Cancer & Hematology Centers of Western Michigan ( Site 0018) Grand Rapids Michigan
HealthPartners Cancer Research Center-HealthPartners Frauenshuh Cancer Center ( Site 0005) Saint Louis Park Minnesota
Regions Hospital ( Site 0095) Saint Paul Minnesota
University of Mississippi Medical Center ( Site 0037) Jackson Mississippi
Dartmouth Hitchcock Medical Center ( Site 0075) Lebanon New Hampshire
Roswell Park Cancer Institute ( Site 0032) Buffalo New York
R.J. Zuckerberg Cancer Center-Medical Oncology ( Site 0013) Lake Success New York
Sidney Kimmel Center for Prostate and Urologic Cancers ( Site 0055) New York New York
Oregon Health & Science University ( Site 0071) Portland Oregon
Ralph H. Johnson VA Center ( Site 0073) Charleston South Carolina
University of Tennessee Medical Center Knoxville ( Site 0019) Knoxville Tennessee
Vanderbilt University Medical Center ( Site 0069) Nashville Tennessee
UTSW Medical Center ( Site 0015) Dallas Texas
Central Washington Health Services Association d/b/a Confluence Health ( Site 0061) Wenatchee Washington
Liverpool Hospital ( Site 4006) Liverpool New South Wales
Macquarie University ( Site 4007) Macquarie University New South Wales
Lyell McEwin Hospital ( Site 4004) Elizabeth Vale South Australia
Monash Health ( Site 4008) Clayton Victoria
Fiona Stanley Hospital ( Site 4009) Murdock Western Australia
Oncocentro Ceara ( Site 0309) Fortaleza Ceará
Centro de Pesquisas Clinicas em Oncologia ( Site 0306) Cachoeiro de Itapemirim Espírito Santo

+ 222 more sites — see the full list on the official registry below.

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT04736706 on ClinicalTrials.gov ↗ ← All trials in the UK