This Phase III trial is evaluating how safe and effective combinations of immunotherapy (pembrolizumab) and targeted therapies (lenvatinib, quavonlimab, belzutifan) are in people with advanced clear cell renal cell carcinomaAn Open-label, Randomized Phase 3 Study to Evaluate Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or MK-1308A in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, as First-Line Treatment in Participants With Advanced Clear Cell Renal Cell Carcinoma (ccRCC)

Exclusion

• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has had major surgery, other than nephrectomy within 4 weeks prior to randomization
• Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has received prior radiotherapy within 2 weeks prior to first dose of study intervention
• Has hypoxia or requires intermittent supplemental oxygen or requires chronic supplemental oxygen
• Has clinically significant cardiac disease within 12 months from first dose of study intervention
• Has a history of interstitial lung disease
• Has symptomatic pleural effusion; a participant who is clinically stable following treatment of this condition is eligible
• Has preexisting gastrointestinal or non-gastrointestinal fistula
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
• Has a known psychiatric or substance abuse disorder that would interfere with requirements of the study
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug; killed vaccines are allowed
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• Has a history of noninfectious pneumonitis that required steroids or has current pneumonitis
• Has an active infection requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a known history of Hepatitis B
• Has radiographic evidence of intratumoral cavitation, encasement or invasion of a major blood vessel
• Has clinically significant history of bleeding within 3 months prior to randomization
• Has had an allogenic tissue/solid organ transplant