A Study of Belzutifan (MK-6482) as Monotherapy and in Combination With Lenvatinib (E7080/MK-7902) With or Without Pembrolizumab (MK-3475) in China Participants With Advanced Renal Cell Carcinoma (MK-6482-010)

NCT ID: NCT05030506

Last Updated: 2025-12-18

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

PHASE1

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-13

Study Completion Date

2027-06-30

Brief Summary

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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profiles, and preliminary efficacy of belzutifan as monotherapy followed by belzutifan+lenvatinib combination therapy, as well as belzutifan combined with lenvatinib and pembrolizumab in China participants with advanced renal cell carcinoma.

Detailed Description

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Conditions

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Renal Cell Carcinoma

Keywords

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Belzutifan Pembrolizumab Programmed Cell Death-1 (PD1) Hypoxia inducible factor 2 alpha (HIF-2 alpha) Hypoxia inducible factor 2α (HIF-2α) Renal Cell Carcinoma (RCC) Kidney Cancer MK-6482 MK6482 PT-2977 PT2977 MK-3475 KEYTRUDA® MK-7902 E7080 LENVIMA®

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Belzutifan + Lenvatinib

Participants will receive a daily oral dose of 120 mg of belzutifan monotherapy for 3 weeks, followed by a combination of a daily oral dose of 120 mg of belzutifan with a daily oral dose of 20 mg of lenvatinib until progressive disease or discontinuation.

Group Type EXPERIMENTAL

Belzutifan

Intervention Type DRUG

40 mg tablet administered orally at a dose of 120 mg

Lenvatinib

Intervention Type DRUG

10 mg capsule administered orally at a dose of 20 mg

Belzutifan + Lenvatinib + Pembrolizumab

Participants will receive an intravenous dose of 400 mg of pembrolizumab once every six weeks for up to 18 infusions (up to 2 years) in combination with a daily oral dose of 120 mg of belzutifan and a daily oral dose of 20 mg of lenvatinib until progressive disease or discontinuation.

Group Type EXPERIMENTAL

Belzutifan

Intervention Type DRUG

40 mg tablet administered orally at a dose of 120 mg

Pembrolizumab

Intervention Type BIOLOGICAL

25 mg/mL solution for Infusion in a single-dose vial administered intravenously at a dose of 400 mg

Lenvatinib

Intervention Type DRUG

10 mg capsule administered orally at a dose of 20 mg

Interventions

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Belzutifan

40 mg tablet administered orally at a dose of 120 mg

Intervention Type DRUG

Pembrolizumab

25 mg/mL solution for Infusion in a single-dose vial administered intravenously at a dose of 400 mg

Intervention Type BIOLOGICAL

Lenvatinib

10 mg capsule administered orally at a dose of 20 mg

Intervention Type DRUG

Other Intervention Names

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MK-6482 PT2977 MK-3475 KEYTRUDA® MK-7902 E7080 LENVIMA®

Eligibility Criteria

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Inclusion Criteria

* Has a histologically confirmed diagnosis of unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC).
* Has measurable disease per RECIST 1.1.
* Has adequate organ function.
* Has adequately controlled blood pressure (BP).
* If participants received major surgery or radiation therapy of \>30 Gy, they must have recovered from the toxicity and/or complications from the intervention.
* Has resolution of the toxic effect(s) of the most recent prior therapy.
* Participants receiving bone resorptive therapy must have therapy initiated at least 2 weeks prior to allocation.
* Is Chinese descent, defined as both biological parents and all biological grandparents are of Chinese descent.

Male Participants:

\- Must be willing to use an adequate method of contraception.

Female Participants:

\- Must be a woman of non-childbearing potential (WONCBP) or have a negative urine or serum pregnancy test and must be willing to use an adequate method of contraception.

For Belzutifan + Lenvatinib treatment:

* Has progressed on or after having received systemic treatment for locally advanced or metastatic RCC.
* Has no more than 3 prior systemic regimens for locally advanced or metastatic RCC.

For Belzutifan + Lenvatinib + Pembrolizumab treatment:

\- Has received no prior systemic therapy for advanced RCC.

Exclusion Criteria

* Is a woman of childbearing potential (WOCBP) who has a positive urine pregnancy test within 24 hours prior to first dose of study intervention.
* Has any of the following: A pulse oximeter reading \<92%, or requires intermittent supplemental oxygen, or requires chronic supplemental oxygen.
* Has a 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 clinically significant cardiac disease.
* Has symptomatic pleural effusion.
* Has a history of inflammatory bowel disease.
* Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula.
* Has clinically significant hematuria, hematemesis or hemoptysis of red blood, or other history of significant bleeding within 3 months before administration of the first dose of study intervention.
* Has other clinically significant disorders such as: A serious active non-healing wound/ulcer/bone fracture, requirement for hemodialysis or peritoneal dialysis or a history of allogenic tissue/solid organ transplantation.
* Received colony-stimulating factors, granulocyte macrophage colony-stimulating factor (GMCSF) or recombinant EPO within 28 days prior to the first dose of study intervention.
* Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
* Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption.
* Has received prior treatment with belzutifan.
* Has received prior treatment with lenvatinib.
* Has received any type of systemic anticancer antibody (including investigational antibody) ≤28 days prior to allocation.
* Has received / will be receiving any traditional Chinese medicines.
* Has received prior radiotherapy within 2 weeks prior to first dose of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.
* Is receiving concomitant treatment, in therapeutic doses, with anticoagulants.
* Is receiving chronic systemic steroids therapy (at doses \>10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.
* Is currently participating in a study of an investigational agent or is currently using an investigational device.
* Has an active infection requiring systemic therapy.
* Has a known history of Human Immunodeficiency Virus (HIV) infection.
* Has a known history of Hepatitis B or known active Hepatitis C virus infection.
* Has a known history of active tuberculosis.
* Has radiographic evidence of intratumoral cavitation, encasement or invasion of a major blood vessel.
* Has known hypersensitivity or allergy to the active pharmaceutical ingredient or any component of the study intervention (belzutifan or lenvatinib) formulations.
* Has had major surgery within 4 weeks prior to first dose of study intervention.

For Belzutifan + Lenvatinib + Pembrolizumab treatment:

* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
* Has a history of hypersensitivity reaction to the active pharmaceutical ingredient or any component of pembrolizumab or monoclonal antibody (mAb).
* Has an active autoimmune disease that has required systemic treatment in the past 2 years.
* Has received a live vaccine within 30 days prior to the first dose of study intervention.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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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-Digestive Oncology ( Site 0001)

Beijing, Beijing Municipality, China

Site Status

SUN YAT-SEN UNIVERSITY CANCER CENTRE-Urology Surgery Department ( Site 0005)

Guangzhou, Guangdong, China

Site Status

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

Nanjing, Jiangsu, China

Site Status

Tianjin Medical University Cancer Institute and Hospital ( Site 0003)

Tianjin, Tianjin Municipality, China

Site Status

The Second Affiliated hospital of Zhejiang University school of medicine-Urology ( Site 0007)

Hangzhou, Zhejiang, China

Site Status

Countries

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China

Related Links

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https://www.merckclinicaltrials.com/

Merck Clinical Trials Information

Other Identifiers

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MK-6482-010

Identifier Type: OTHER

Identifier Source: secondary_id

6482-010

Identifier Type: -

Identifier Source: org_study_id