• Has the ability to understand and willingness to sign a written ICF before the performance of any study-specific procedures on this protocol and 2022-0515

• Age ≥ 18 years

• Has locally advanced or metastatic RCC with predominantly clear cell subtype

• Has at least one measurable lesion as defined by RECIST version 1.1

• Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1

• Has adequate organ function defined as follows:

• a. Absolute neutrophil count ≥ 1,500/µL, Hgb level ≥ 9 g/dL and platelet count (Plt) i. ≥ 100,000/µL without transfusion or growth factor support within 2 weeks prior to obtaining the hematology values at screening; b. Creatinine clearance ≥ 40 mL/min/1.73m2 c. Transaminase levels (AST/ALT) ≤ 3.0 × upper limit of normal (ULN); total bilirubin i. (TBILI) ≤ 1.5 mg/dL in the absence of Gilbert's disease

• Women of child beariring potential must have a negative serum preganancy test within 7 days before first study drug administration

• Female patients of child bearing potential, or a male patients with a female partner of child-bearing potential (defined as all women physiologically capable of becoming pregnant), must agree to use a highly effective method of contraception during screening, during the period of drug administration and for 120 days after stopping study drug administration. Highly effective contraception methods include the following:

∙ Total abstinence (defined as refraining from heterosexual intercourse during the entire period outlined above),

‣ Male or female sterilization, or

• Use of at least one of the following:

• Use of oral, injectable, transdermal, intravaginal, or implantable hormonal methods of contraception i. Combined estrogen and progestogen containing hormonal contraception associated with inhibition of ovulation ii. Progestogen-only hormonal contraception associated with inhibition of ovulation c. Placement of an intrauterine device or intrauterine system

• Able to swallow oral medications

⁃ Able to provide tumor tissue sample (archival or recent acquisition)

⁃ Patients with brain metastases are eligible providing other measurable disease exists and brain lesions are controlled for one month (requiring no therapy) and are not life threatening.