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)

• Status: Recruiting
• Trial end date: 2025-04-25
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Merck Sharp & Dohme Corp.
• Treatments: Lenvatinib; Pembrolizumab

Criteria

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: Hypoxia, 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 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.

• Have received / be receiving any traditional Chinese medicines or herbal supplements.

• 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.