A Study of Belzutifan (MK-6482) in Participants With Advanced Renal Cell Carcinoma (MK-6482-013)

Inclusion Criteria:

• Has a histologically confirmed diagnosis of locally advanced/metastatic RCC withclear cell component

• Has measurable disease per RECIST 1.1 as assessed by BICR

• Can submit an archival tumor tissue sample or newly obtained core or excisionalbiopsy of a tumor lesion not previously irradiated

• Has experienced disease progression on or after systemic treatment with ananti-programmed cell death 1 (PD-1)/Ligand 1 (L1) therapy for locally advanced ormetastatic RCC. The anti-PD-1/L1 therapy may be monotherapy or in combination withother agent(s) such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) orvascular endothelial growth factor (VEGF) targeted- tyrosine kinase inhibitor (TKI).The immediately preceding line of treatment has to have been an anti-PD-1/L1 therapy

• Has received no more than 3 prior systemic regimens for locally advanced ormetastatic RCC

• Has received only 1 prior anti-PD-1/L1 therapy for locally advanced or metastaticRCC

• Has recovered from all AEs due to previous therapies to ≤Grade 1 or baseline, withthe exception of ≤Grade 2 neuropathy or endocrine-related AEs ≤Grade 2 requiringtreatment or hormone replacement

• Has a Karnofsky performance status (KPS) score of at least 70% assessed within 10days prior to the first dose of study intervention

• A male participant is eligible to participate if he is abstinent from heterosexualintercourse or agrees to use contraception during the intervention period and for atleast 7 days after the last dose of study intervention

• A female participant is eligible to participate if she is not pregnant, notbreastfeeding, and at least 1 of the following conditions applies: Not a (woman ofchildbearing potential) WOCBP or a WOCBP who agrees to follow the contraceptiveguidance during the intervention period and for at least 30 days after the last doseof study intervention

• A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) within 24 hours before the first dose of study intervention

Exclusion Criteria:

• Has hypoxia (a pulse oximeter reading <92% at rest), requires intermittentsupplemental oxygen, or requires chronic supplemental oxygen

• Has a known additional malignancy that is progressing or has required activetreatment within the past 3 years except for basal cell carcinoma of the skin,squamous cell carcinoma of the skin, or carcinoma in situ [e.g., breast carcinoma,cervical cancer in situ] that have undergone potentially curative therapy

• Has known central nervous system (CNS) metastases and/or carcinomatous meningitis

• Has clinically significant cardiac disease, including unstable angina, acutemyocardial infarction ≤6 months from Day 1 of study drug administration or New YorkHeart Association Class III or IV congestive heart failure

• Has moderate to severe hepatic impairment (Child-Pugh B or C)

• Has received colony-stimulating factors (eg, granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], or recombinanterythropoietin [EPO]) ≤28 days prior to the first dose of study intervention

• Has a known psychiatric or substance abuse disorder that would interfere withcooperation with the requirements of the study

• Is unable to swallow orally administered medication or has a gastrointestinaldisorder affecting absorption (eg, gastrectomy, partial bowel obstruction,malabsorption)

• Has known hypersensitivity or allergy to the active pharmaceutical ingredient or anycomponent of the study intervention (belzutifan) formulations

• Has received prior treatment with belzutifan or another hypoxia-inducible factor (HIF)-2α inhibitor

• Has received any type of small molecule kinase inhibitor (including investigationalkinase inhibitor) ≤2 weeks before randomization

• Has received any type of systemic anticancer antibody (including investigationalantibody) ≤4 weeks before randomization

• Has received prior radiotherapy ≤2 weeks prior to first dose of study intervention.Participants must have recovered from all radiation-related toxicities and notrequire corticosteroids

• Has had major surgery ≤3 weeks prior to first dose of study intervention

• Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin,rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) ormoderate (eg, bosentan, efavirenz, modafinil) inducers of cytochrome P450 (CYP)3A4that cannot be discontinued for the duration of the study

• Is currently participating in a study of an investigational agent or is currentlyusing an investigational device

• Has an active infection requiring systemic therapy

• Has active tuberculosis (TB)

• Has a diagnosis of immunodeficiency

• Has a known history of human immunodeficiency virus (HIV) infection

• Has a known history of hepatitis B (HBV) or known active hepatitis C (HCV) infection

• Has a history or current evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the study, interfere with theparticipant's participation for the full duration of the study, or is not the bestinterest of the participant to participate, in the opinion of the treatinginvestigator