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

NCT ID: NCT05899049

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

249 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-27

Study Completion Date

2027-06-07

Brief Summary

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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.

Detailed Description

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The China extension study will include participants previously enrolled in China in the global study for MK-6482-012 (NCT04736706) plus those enrolled during the China extension enrollment period. A total of approximately 249 Chinese participants will be enrolled.

Conditions

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Carcinoma, Renal Cell

Keywords

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Programmed Cell Death-1 (PD1, PD-1) Programmed Death-Ligand 1 (PDL1, PD-L1) Hypoxia inducible factor (HIF) Hypoxia inducible factor 1B (HIF-1B) Hypoxia inducible factor 2 alpha (HIF-2 alpha)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Pembrolizumab + Belzutifan + Lenvatinib

Participants 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.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

Pembrolizumab 400 mg administered Q6W via IV infusion

Belzutifan

Intervention Type DRUG

Belzutifan 120 mg administered QD via oral tablet

Lenvatinib

Intervention Type DRUG

Lenvatinib 20 mg administered QD via oral capsule

Pembrolizumab/Quavonlimab + Lenvatinib

Participants 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.

Group Type EXPERIMENTAL

Pembrolizumab/Quavonlimab

Intervention Type BIOLOGICAL

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

Lenvatinib

Intervention Type DRUG

Lenvatinib 20 mg administered QD via oral capsule

Pembrolizumab + Lenvatinib

Participants 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.

Group Type ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type BIOLOGICAL

Pembrolizumab 400 mg administered Q6W via IV infusion

Lenvatinib

Intervention Type DRUG

Lenvatinib 20 mg administered QD via oral capsule

Interventions

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Pembrolizumab

Pembrolizumab 400 mg administered Q6W via IV infusion

Intervention Type BIOLOGICAL

Belzutifan

Belzutifan 120 mg administered QD via oral tablet

Intervention Type DRUG

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

Intervention Type BIOLOGICAL

Lenvatinib

Lenvatinib 20 mg administered QD via oral capsule

Intervention Type DRUG

Other Intervention Names

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MK-3475 KEYTRUDA® MK-6482 PT2977 WELIREG™ MK-1308A MK-7902 E7080 LENVIMA®

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eisai Inc.

INDUSTRY

Sponsor Role collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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Beijing Cancer hospital-Renal carcinoma and melanoma ( Site 6000)

Beijing, Beijing Municipality, China

Site Status

Chongqing University Cancer Hospital ( Site 6009)

Chongqing, Chongqing Municipality, China

Site Status

SUN YAT-SEN UNIVERSITY CANCER CENTRE ( Site 6003)

Guangzhou, Guangdong, China

Site Status

The First Affiliated Hospital of Guangzhou Medical University-Urology ( Site 6036)

Guangzhou, Guangdong, China

Site Status

Guangzhou First People's Hospital ( Site 6007)

Guangzhou, Guangdong, China

Site Status

Henan Cancer Hospital-Urology ( Site 6006)

Zhengzhou, Henan, China

Site Status

Wuhan Union Hospital ( Site 6002)

Wuhan, Hubei, China

Site Status

Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School-Urology ( S

Nanjing, Jiangsu, China

Site Status

The Second Affiliated Hospital of Soochow University-Urology ( Site 6025)

Suzhou, Jiangsu, China

Site Status

The First Affiliated Hospital of Nanchang University ( Site 6019)

Nanchang, Jiangxi, China

Site Status

The First Affiliated Hospital of Xi'an Jiaotong University ( Site 6014)

Xi'an, Shaanxi, China

Site Status

West China Hospital Sichuan University-Urology Surgery ( Site 6016)

Chengdu, Sichuan, China

Site Status

The Second Hospital of Tianjin Medical University ( Site 6032)

Tianjin, Tianjin Municipality, China

Site Status

The First Affiliated Hospital, Zhejiang University ( Site 6024)

Hangzhou, Zhejiang, China

Site Status

The First Hospital of Jiaxing ( Site 6033)

Jiaxing, Zhejiang, China

Site Status

Ningbo First Hospital-Urology ( Site 6028)

Ningbo, Zhejiang, China

Site Status

The First Affiliated Hospital of Wenzhou Medical University-Urology Surgery ( Site 6021)

Wenzhou, Zhejiang, China

Site Status

Countries

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China

Related Links

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https://merckclinicaltrials.com/

Merck Clinical Trials Information

Other Identifiers

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MK-6482-012 China Extension

Identifier Type: OTHER

Identifier Source: secondary_id

jRCT2031210435

Identifier Type: REGISTRY

Identifier Source: secondary_id

PHRR210911-003887

Identifier Type: REGISTRY

Identifier Source: secondary_id

6482-012 China Extension

Identifier Type: -

Identifier Source: org_study_id