Intermittent Therapy in Metastatic Renal Cell Carcinoma Patients Treated With Ipilimumab and Nivolumab

Inclusion Criteria: * Cohort 1: * Must have received at least one but not more than two prior anti-angiogenic therapy regimens (including, but not limited to, sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and bevacizumab) in the advanced or metastatic RCC setting. Prior cytokine therapy (eg, IL-2, IFN-a), vaccine therapy, or treatment with cytotoxics is also allowed. * No more than three total prior systemic treatment regimens in the advanced or metastatic RCC setting. * Cohort 2: --Achieved SD, PR, or CR after administration of front-line therapy with Ipi/Nivo (up to 4 doses) for advanced/metastatic RCC followed by 24 weeks (+/- 8 weeks; minimum 3 infusions) of Nivo maintenance. Patient enrollment will occur after completion of 24 weeks (+/- 8 weeks; minimum 3 infusions) of maintenance nivolumab. * Histological confirmation of renal cell carcinoma (RCC) (any histology) * Advanced or metastatic RCC. * Measurable disease as defined by RECIST 1.1 criteria * Must have received at least one but not more than two prior anti-angiogenic therapy regimens (including, but not limited to, sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and bevacizumab) in the advanced or metastatic RCC setting. Prior cytokine therapy (for example, Interleukin (IL)-2, interferon (IFN)-α), vaccine therapy, or treatment with cytotoxics is also allowed. * Patients treated with neoadjuvant and/or adjuvant therapy prior to development of metastatic disease may also be included provided that at least 12 months have elapsed since last dose. These regimens do not count toward total number of prior therapies permitted for trial inclusion. * No more than three total prior systemic treatment regimens in the advanced or metastatic RCC setting, and must have evidence of progression on or after the last treatment regimen received and within 6 months prior to study enrollment. * Karnofsky Performance Score (KPS) ≥70% * Women of childbearing potential (WOCBP) must use effective method(s) of contraception have a negative serum or urine pregnancy test within 24 hours prior to the start of therapy, and must not be breastfeeding. Pregnant women are excluded from this study because animal studies have demonstrated that nivolumab can cause fetal harm when administered to pregnant women. Breastfeeding women are excluded from this study because nivolumab may be excreted in human milk and the potential for serious adverse reactions in nursing infants. * Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year * Willing and able to provide informed consent. * Laboratory criteria for study entry must meet the following criteria: * Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 40 mL/min (measured or calculated using the Cockcroft-Gault formula). * white blood cell count ≥ 2000/µL * Neutrophils ≥ 1500/µL * Platelets ≥ 100,000/µL * Hemaglobin ≥ 9.0g/dL * Aspartate Aminotransferase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN * Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL) Exclusion Criteria: * Cohort 1 only: --Prior treatment with an anti-programmed death (PD)-1, anti-programmed death ligand 1 (PD-L1), anti-programmed death ligand 2 (PD-L2), anti-Cluster of differentiation (CD137), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. * Anti-cancer therapy less than 14 days prior to the first dose of study drug (less than 28 days for bevacizumab) or palliative, focal radiation therapy less than 14 days prior to the first dose of study drug. * History of severe hypersensitivity reaction to any monoclonal antibody. * Patients are excluded if they have active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if metastases have been treated and there is no imaging evidence of progression for 28 days after treatment is complete and within 28 days prior to the first dose of nivolumab administration. * Major surgery (eg, nephrectomy) less than 28 days prior to the first dose of study drug. * Any active known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition or prior therapy requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. * Any condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose of study drug. Inhaled steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease. * Any known active chronic liver disease. * Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). * Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection. * Known medical condition (for example, a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results. * Strong Cytochrome P450 3A4 (CYP3A4) inhibitors