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)

NCT05030506 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 6482-010MK-6482-010
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Renal Cell Carcinoma

Keywords

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®

Outcome Measures

Primary Outcomes (14)

• Number of participants who experienced dose-limiting toxicities (DLTs)

  A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0). Number of participants who experience a DLT per CTCAE 5.0 will be reported.

  Up to approximately 21 days

• Number of participants who experienced an adverse event (AE)

  An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experience an AE in the study will be reported.

  Up to approximately 68 months

• Number of participants who discontinued study treatment due to an AE

  An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinued from the study treatment due to an AE will be reported.

  Up to approximately 68 months

• Area under the concentration-time curve from 0-24 hours (AUC0-24) of belzutifan after single dose (Cohort 1)

  AUC is a measure of plasma drug concentration and time and is estimated as the area under the plot of plasma concentration against time after drug administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine AUC0-24 of belzutifan.

  Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

• Maximum concentration (Cmax) of belzutifan after single dose (Cohort 1)

  Cmax is the maximum concentration of the drug observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax of belzutifan.

  Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

• Time at maximum concentration (Tmax) of belzutifan after single dose (Cohort 1)

  Tmax is the amount of time that a drug is present at the maximum concentration is observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the Tmax of belzutifan.

  Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

• Steady state area under the concentration-time curve from 0-24 hours (AUC0-24,ss) of belzutifan after multiple doses (Cohort 1)

  AUC0-24,ss is a measure of plasma drug concentration and time and is estimated as the area under the plot of plasma concentration against time after drug administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine AUC0-24,ss of belzutifan.

  Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

• Steady state maximum concentration (Cmax,ss) of belzutifan after multiple doses (Cohort 1)

  Cmax,ss is the maximum concentration of the drug observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax,ss of belzutifan.

  Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

• Time at maximum concentration (Tmax) of belzutifan after multiple doses (Cohort 1)

  Tmax is the amount of time that a drug is present at the maximum concentration is observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the Tmax of belzutifan.

  Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

• Apparent t½ of belzutifan after multiple doses (Cohort 1)

  T1/2 is a measure of how long it takes to clear 50% of the drug after reaching Cmax. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine t1/2 of belzutifan.

  Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose.

• Steady state trough concentration (Ctrough,ss) of belzutifan after multiple doses (Cohort 1)

  Ctrough,ss is the lowest concentration reached by a drug before the next dose is administered. Blood samples taken at predose and at specified times post dose will be used to determine Ctrough,ss of belzutifan.

  Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

• Accumulation ratio (RAC) of belzutifan after multiple doses (Cohort 1)

  RAC is the ratio of accumulation of a drug under steady state conditions after repeated administration as compared to a single dose. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine RAC of belzutifan.

  Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

• Apparent oral clearance (CL/F) of belzutifan after multiple doses (Cohort 1)

  CL/F is the apparent total clearance of the drug from plasma after oral administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine CL/F of belzutifan.

  Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

• Apparent oral volume (Vz/F) of belzutifan after multiple doses (Cohort 1)

  Vz/F is the apparent volume of distribution of the drug during terminal phase after non-intravenous administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Vz/F of belzutifan.

  Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Secondary Outcomes (9)

• Objective response rate (ORR)

  Up to approximately 68 months

• Duration of response (DOR)

  Up to approximately 68 months

• Progression-free survival (PFS)

  Up to approximately 68 months

• Overall survival (OS)

  Up to approximately 68 months

• Steady state trough concentration (Ctrough,ss) of belzutifan (Cohort 2)

  Pre-dose, and 1, 2 and 4 hours postdose

Study Arms (2)

Belzutifan + Lenvatinib

EXPERIMENTAL

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.

Drug: Belzutifan; Drug: Lenvatinib

Belzutifan + Lenvatinib + Pembrolizumab

EXPERIMENTAL

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.

Drug: Belzutifan; Biological: Pembrolizumab; Drug: Lenvatinib

Interventions

Lenvatinib DRUG

10 mg capsule administered orally at a dose of 20 mg

Also known as: MK-7902, E7080, LENVIMA®

Belzutifan + Lenvatinib; Belzutifan + Lenvatinib + Pembrolizumab

Belzutifan DRUG

40 mg tablet administered orally at a dose of 120 mg

Also known as: MK-6482, PT2977

Belzutifan + Lenvatinib; Belzutifan + Lenvatinib + Pembrolizumab

Pembrolizumab BIOLOGICAL

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

Also known as: MK-3475 KEYTRUDA®

Belzutifan + Lenvatinib + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (5)

Beijing Cancer hospital-Digestive Oncology ( Site 0001)

Beijing, Beijing Municipality, 100142, China

Location

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

Guangzhou, Guangdong, 510060, China

Location

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

Nanjing, Jiangsu, 210000, China

Location

Tianjin Medical University Cancer Institute and Hospital ( Site 0003)

Tianjin, Tianjin Municipality, 300060, China

Location

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

Hangzhou, Zhejiang, 310052, China

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

belzutifan; pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2021
• First Posted: September 1, 2021
• Study Start: October 13, 2021
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

CN (5)