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, vs Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012)-China Extension Study
An Open-label, Randomized Phase 3 Study to Evaluate Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or MK-1308A in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, as First-Line Treatment in Participants With Advanced Clear Cell Renal Cell Carcinoma (ccRCC)
4 other identifiers
interventional
249
1 country
17
Brief Summary
The goal of this China extension 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 Chinese 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jul 2022
Longer than P75 for phase_3
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 27, 2022
CompletedFirst Submitted
Initial submission to the registry
June 2, 2023
CompletedFirst Posted
Study publicly available on registry
June 12, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 7, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 7, 2027
November 10, 2025
October 1, 2025
4.9 years
June 2, 2023
November 6, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR based on RECIST 1.1 will be presented.
Up to approximately 58 months
Overall Survival (OS)
OS is defined as the time from randomization to death due to any cause.
Up to approximately 58 months
Secondary Outcomes (4)
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR
Up to approximately 58 months
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
Up to approximately 58 months
Number of Participants Who Experienced At least One Adverse Event (AE)
Up to approximately 58 months
Number of Participants Who Discontinue Study Treatment Due to an AE
Up to approximately 58 months
Study Arms (3)
Pembrolizumab + Belzutifan + Lenvatinib
EXPERIMENTALParticipants will receive pembrolizumab 400 mg PLUS belzutifan 120 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered intravenously (IV) once every 6 weeks (Q6W) for up to 18 administrations (up to \~2 years). Belzutifan and lenvatinib will be administered orally once daily (QD) until progressive disease or discontinuation.
Pembrolizumab/Quavonlimab + Lenvatinib
EXPERIMENTALParticipants will receive pembrolizumab/quavonlimab (co-formulation of pembrolizumab 400 mg and quavonlimab 25 mg) PLUS lenvatinib 20 mg. Pembrolizumab/quavonlimab will be administered IV Q6W for up to 18 administrations (up to \~2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.
Pembrolizumab + Lenvatinib
ACTIVE COMPARATORParticipants will receive pembrolizumab 400 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered IV Q6W for up to 18 administrations (up to \~2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.
Interventions
Pembrolizumab 400 mg administered Q6W via IV infusion
Belzutifan 120 mg administered QD via oral tablet
Pembrolizumab/quavonlimab is a co-formulated product composed of pembrolizumab 400 mg in combination with quavonlimab 25 mg, administered Q6W via IV infusion
Lenvatinib 20 mg administered QD via oral capsule
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Merck Sharp & Dohme LLClead
- Eisai Inc.collaborator
Study Sites (17)
Beijing Cancer hospital-Renal carcinoma and melanoma ( Site 6000)
Beijing, Beijing Municipality, 100142, China
Chongqing University Cancer Hospital ( Site 6009)
Chongqing, Chongqing Municipality, 400030, China
SUN YAT-SEN UNIVERSITY CANCER CENTRE ( Site 6003)
Guangzhou, Guangdong, 510060, China
The First Affiliated Hospital of Guangzhou Medical University-Urology ( Site 6036)
Guangzhou, Guangdong, 510120, China
Guangzhou First People's Hospital ( Site 6007)
Guangzhou, Guangdong, 510180, China
Henan Cancer Hospital-Urology ( Site 6006)
Zhengzhou, Henan, 450008, China
Wuhan Union Hospital ( Site 6002)
Wuhan, Hubei, 430022, China
Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School-Urology ( S
Nanjing, Jiangsu, 210000, China
The Second Affiliated Hospital of Soochow University-Urology ( Site 6025)
Suzhou, Jiangsu, 215004, China
The First Affiliated Hospital of Nanchang University ( Site 6019)
Nanchang, Jiangxi, 330006, China
The First Affiliated Hospital of Xi'an Jiaotong University ( Site 6014)
Xi'an, Shaanxi, 710061, China
West China Hospital Sichuan University-Urology Surgery ( Site 6016)
Chengdu, Sichuan, 610041, China
The Second Hospital of Tianjin Medical University ( Site 6032)
Tianjin, Tianjin Municipality, 300211, China
The First Affiliated Hospital, Zhejiang University ( Site 6024)
Hangzhou, Zhejiang, 310003, China
The First Hospital of Jiaxing ( Site 6033)
Jiaxing, Zhejiang, 314001, China
Ningbo First Hospital-Urology ( Site 6028)
Ningbo, Zhejiang, 315010, China
The First Affiliated Hospital of Wenzhou Medical University-Urology Surgery ( Site 6021)
Wenzhou, Zhejiang, 325000, China
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Medical Director
Merck Sharp & Dohme LLC
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 2, 2023
First Posted
June 12, 2023
Study Start
July 27, 2022
Primary Completion (Estimated)
June 7, 2027
Study Completion (Estimated)
June 7, 2027
Last Updated
November 10, 2025
Record last verified: 2025-10
Data Sharing
- IPD Sharing
- Will share
https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf