Genetic Testing to Select Therapy for the Treatment of Advanced or Metastatic Kidney Cancer, OPTIC RCC Study

PRIMARY OBJECTIVE: I. To improve objective response rate of front-line therapy in advanced renal cell carcinoma (RCC) by prospectively assigning ipilimumab/nivolumab or nivolumab/cabozantinib according to a patient's ribonucleic acid sequence (RNAseq)-defined biologic cluster. SECONDARY OBJECTIVE: I. To assess clinical outcome of cluster-assigned treatment in front-line metastatic renal cell carcinoma (mRCC). EXPLORATORY OBJECTIVE: I. To assess tissue and peripheral blood for pharmacodynamic correlations with response to treatment. OUTLINE: Patients are assigned to 1 of 2 arms. ARM I: INDUCTION: Patients receive ipilimumab and nivolumab intravenously (IV) on day 1. Cycles repeat every 21 days for 4 cycles. MAINTENANCE: Patients receive nivolumab IV on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive nivolumab IV on day 1 and cabozantinib orally (PO) once a day (QD). Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up within 30 days from last dose.