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)

Conditions: Renal Cell Carcinoma

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.


Eligibility 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: 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.

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®