• Patient must have ECOG PS of ≤ 2 within 28 days of C1D1.

• Age ≥ 18 years old at the time of informed consent.

• Patient must have histological confirmation of renal carcinoma with clear cell component including advanced RCC (not amenable to curative surgery or radiation therapy) or metastatic RCC.

• Patient must have measurable disease by CT or MRI per RECIST 1.1 criteria. Radiated lesions cannot be used as measurable lesions unless there is clear evidence of progression.

• Patient must have defined IMDC risk categorization of either favorable, intermediate or poor based on clinical variables of increased risk (below).

‣ No risk factors (0) = favorable risk

⁃ 1-2 risk factors = intermediate risk

⁃ ≥ 3 risk factors = poor risk

• NOTE: Patients with all IMDC risk factors are eligible, but will be stratified according to IMDC risk, and initial analysis will be based on the IMDC intermediate and poor risk patients. IMDC Risks:

⁃ KPS less than 80%

⁃ Less than 1 year from diagnosis including original localized disease to randomization(if applicable)

⁃ Hemoglobin less than the lower limit of normal

⁃ Corrected calcium concentration greater than 10 mg/dL

⁃ ANC greater than the ULN

⁃ Platelet count greater than the ULN

• Patient must have either a formalin-fixed, paraffin-embedded (FFPE) tissue block or at least 10 (preferably 20) unstained tumor tissue sections, obtained from a metastatic lesion, preferably within 3 months or no more than 12 months with an associated pathology report. This tissue must be identified prior to registration. Confirmation of sufficient archival tissue must be obtained after informed consent and the tissue must be shipped to the appropriate lab by end of Cycle 2. Biopsies should be excisional, incisional, or core needle. Fine needle aspiration is unacceptable for submission. Biopsies of bone lesions that do not have a soft tissue component are also unacceptable for submission. This sample is required to be eligible for the trial. If a patient is having a standard of care biopsy, part of that sample may be utilized for eligibility.

• Demonstrate adequate organ function as defined below; all screening labs to be obtained within 28 days prior to registration.

‣ Hematological

⁃ White blood cell (WBC) ≥ 2,000/uL

⁃ Absolute Neutrophil Count (ANC) ≥ 1,000/uL; without growth factor support

⁃ Hemoglobin (Hgb) ≥ 8.0 g/dL; ≥ 7 days without PRBC transfusion.

⁃ Platelets ≥ 75,000/uL; without platelet transfusion

⁃ Renal

⁃ Calculated creatinine clearance (CrCl)1 ≥ 40 mL/min

⁃ Hepatic

⁃ Total Bilirubin ≤ 1.5 × upper limit of normal (ULN) \*EXCEPT participants with Gilbert Syndrome who must have a Total Bilirubin level of \< 3.0 x ULN

⁃ Aspartate aminotransferase (AST) ≤ 3.0 × ULN

⁃ Alanine aminotransferase (ALT) ≤ 3.0 × ULN

• HIV positive patients may be eligible if either:

‣ Patients with CD4 \> 200 cells/mm3 OR

⁃ Patients with HIV viral load undetectable.

• Active HBV or active HCV patients may be eligible if:

‣ Patients with HBV infection are eligible if hepatitis B surface antigen and HBV DNA are negative.

⁃ Patients with HCV infection are eligible if HCV RNA is negative.

⁃ WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 1 week prior to Cycle 1 Day 1.

⁃ WOCBP must agree to follow instructions for method(s) of contraception.

⁃ Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception.