• Willing and able to provide a signed and dated written informed consent.

• ≥ 18 years of age

• Confirmed diagnosis of RCC with a clear cell component

• Stage IV metastatic renal cell carcinoma per American Joint Committee on Cancer

• No prior systemic therapy for RCC. Prior neo/adjuvant systemic therapy is not allowed.

• Karnofsky performance status ≥ 70%.

• At least one measurable lesion as defined by RECIST 1.1 (Appendix 3)

• • A tumor lesion situated in a previously irradiated area is considered a measurable/target lesion only if subsequent disease progression has been documented in the lesion

• Adequate organ function within 28 days prior to first dose of protocol-indicated treatment, including:

‣ White blood cell (WBC) ≥ 2,000 /µL

⁃ Absolute neutrophil count (ANC) ≥ 1,500/µL

⁃ Platelets ≥ 100,000/µL

⁃ Serum creatinine \< 1.5 x upper limit of normal (ULN) or creatinine clearance \> 30 mL/min (measured or calculated by Cockroft-Gault formula)

⁃ Total bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who must have total bilirubin \< 3.0 mg/dL)

⁃ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN

• Women must not be breastfeeding while taking the study drug and for up to five months after the last dose of study drug

⁃ Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to receiving first dose of protocol-indicated treatment. An extension up to 72 hours prior to the start of study treatment is permissible in situations where results cannot be obtained within the standard 24-hour window.

∙ Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal.

‣ Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 years of age in the absence of other biological or physiological causes.

‣ If menopausal status is considered for the purpose of evaluating childbearing potential, women \< 62 years of age must have a documented serum follicle stimulating hormone (FSH) level within laboratory reference range for postmenopausal women, in order to be considered postmenopausal and not of childbearing potential.

⁃ Women of childbearing potential (WOCBP) must agree to follow instructions for acceptable contraception Appendix 5 from the time of signing consent, and for 23 weeks after their last dose of protocol-indicated treatment.