Study on Combination Therapies for Kidney Cancer That Returns During or After Anti-PD-(L)1 Treatment

The main inclusion criteria include but are not limited to the following:

• Has a histologically confirmed diagnosis of unresectable locally advanced/metastatic renal cell carcinoma (RCC) with clear cell component
• Has received no other prior systemic therapy for treatment of advanced/metastatic clear cell renal cell carcinoma (ccRCC) except for adjuvant programmed cell death ligand 1 (PD-(L)1) therapy
• Has disease recurrence during adjuvant anti- PD-(L)1 therapy or ≤24 months following the last dose of adjuvant anti-PD-(L)1 therapy
• Is able to swallow oral medication
• Submits an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
• Participants receiving bone resorptive therapy (must have therapy initiated at least 2 weeks before allocation/randomization)
• Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤140/90 mm Hg with no change in antihypertensive medications within 1 week before allocation/randomization
• Has adequate organ function

The main exclusion criteria include but are not limited to the following:

• Has clinically significant hematuria, hematemesis, or hemoptysis of (>2.5 mL) of red blood, or other history of significant bleeding
• Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
• Has deep vein thrombosis within 3 months before allocation/randomization unless stable, asymptomatic, and treated with therapeutic anticoagulation for at least 4 weeks before allocation/randomization
• Has history of idiopathic pulmonary fibrosis, organizing pneumonia, or evidence of active pneumonitis
• Has serious wound, ulcer or bone fracture or has had major surgery within 8 weeks before first dose of study intervention
• Has symptomatic pleural effusion (for example cough, dyspnea, pleuritic chest pain), ascites, or pericardial fluid requiring drainage in the last 4 weeks before allocation/randomization
• Has gastrointestinal (GI) disorders, including those associated with a high risk of perforation or fistula formation
• Has malabsorption due to prior GI surgery or GI disease
• Has moderate to severe hepatic impairment
• Has received colony-stimulating factors within 28 days prior to intervention allocation/randomization
• Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
• Is currently receiving strong inhibitors of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of the study
• Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention
• Is currently receiving anticoagulants or platelet inhibitors that cannot be discontinued for the duration of the study
• Have been previously allocated/randomized to study intervention in any sub study of protocol MK-3475-U03
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
• Has active autoimmune disease that has required systemic treatment in the past 2 years
• Has an active infection requiring systemic therapy
• Has history of human immunodeficiency virus (HIV) infection
• Has hepatitis B or hepatitis C virus infection