Background: Therapeutic options have improved outcomes for patients (pts) with metastatic renal cell carcinoma (mRCC). Nivolumab, a fully human IgG4 programmed cell death-1 immune checkpoint inhibitor antibody, has shown clinical activity in RCC and in other tumor types. In CheckMate 016, a phase I study, nivolumab + ipilimumab demonstrated acceptable safety and encouraging antitumor activity in patients with mRCC (Hammers HJ, et al. J Clin Oncol. 2014;3215 suppl]:4504). This phase III study evaluates nivolumab + ipilimumab compared with sunitinib monotherapy for previously untreated mRCC (NCT02231749). Methods: Adults with advanced or metastatic clear-cell RCC with no prior systemic therapy are eligible. Pts with one prior adjuvant/neoadjuvant therapy (excluding VEGF targeted therapies) following RCC resection are eligible if recurrence occurred ≥ 6 months after the last dose. Other key inclusion criteria include: Karnofsky Performance Status ≥ 70%, measurable disease per RECIST v1.1, and available tumor tissue. Pts with a history of, or current, central nervous system metastases are ineligible. Prior treatment with systemic corticosteroids/immunosuppressants within 14 days before first dose of study drug, or with any agent targeting T cell co-stimulation or checkpoint pathways is not permitted. The study is expected to randomize ~1,070 pts stratified by International mRCC Database Consortium prognostic score (0 vs 1–2 vs 3–6) and region (US vs Canada/Europe vs rest of world). Pts will be randomized to either: i) nivolumab 3 mg/kg intravenously (IV) + ipilimumab 1 mg/kg IV every 3 weeks for four doses, followed by nivolumab monotherapy 3 mg/kg IV every 2 weeks or ii) sunitinib 50 mg orally once daily for 4 weeks followed by 2 weeks off. Treatment will be discontinued for unacceptable toxicity or withdrawal of consent. Pts may continue treatment beyond progression (RECIST v1.1) if investigator-assessed clinical benefit is achieved and treatment is well tolerated. The co-primary endpoints are progression-free survival and overall survival. Secondary endpoints include objective response rate and safety. Clinical trial information: NCT02231749