Pre-NEOSHIFT-RCC: Neoadjuvant HIF-Inhibitor Immunotherapy in RCC

Inclusion Criteria: * Adult patients age ≥ 18 years. * Histologically confirmed diagnosis of ccRCC by a core-needle biopsy. Patients who have not had prior biopsy may undergo screening if they have suspected RCC but can only proceed to registration if ccRCC (any component) is confirmed on the pre-treatment study biopsy. * Stage cT2 RCC with grade 4 or sarcomatoid features, ≥cT3 Nx RCC, or cTany N+ RCC disease for which partial or radical nephrectomy is planned. For clinical staging, a kidney MRI is highly preferred over a CT Abdomen. * Participants must have measurable disease i.e. a primary renal tumor that can be accurately measured in at least one dimension as ≥10 mm (≥1 cm) with CT scan or MRI. See Section 11 (Measurement of Effect) for the evaluation of measurable disease. * Participants must be planned for surgical resection of their primary renal tumor. * ECOG performance status of 0-1. * Participants must have adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment: 1. Absolute neutrophil count ≥ 1.0 × 10\^9/L without granulocyte colony-stimulating factor support within 2 weeks of screening laboratory sample collection. 2. Platelet count ≥ 100 × 10\^9/L without transfusion within 2 weeks of screening laboratory sample collection. 3. Hemoglobin ≥ 10.0 g/dL (or 6.2 mmol/L). 4. Aspartate transaminase (AST) ≤ 2.5 × upper limit of normal (ULN) 5. Alanine aminotransferase (ALT) ≤ 2.5 × ULN. 6. Bilirubin ≤ 1.5 × ULN (except participants with Gilbert syndrome who must have total bilirubin \< 3.0 mg/dL). 7. Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. 8. Ambulatory oxygen saturation \>92% on room air at time of screening. 9. Serum albumin ≥ 2.8 g/dl. 10. INR ≤ 1.5. 11. Calculated creatinine clearance ≥ 40 mL/min (≥ 0.67 mL/sec) using the Cockcroft-Gault equation: ---Males: (140 - age) x weight (kg)/(serum creatinine \[mg/dL\] × 72) ---Females: \[(140 - age) x weight (kg)/(serum creatinine \[mg/dL\] × 72)\] × 0.85 * No exercise-induced desaturation on a 6-minute walk test, defined as a blood oxygen saturation by pulse oximetry ≤ 88%. * No active clinical pneumonitis at screening. * No medical history of severe chronic obstructive pulmonary disease (COPD) * Screening echocardiogram or MUGA scan must demonstrate a left ventricular ejection fraction (LVEF) greater than the institutional lower limit of normal (LLN). * Negative serum pregnancy test at screening for women of childbearing potential. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \> 45 years-of-age in the absence of other biological or physiological causes. In addition, females \< 55 years-of-age must have a serum follicle stimulating hormone \[FSH\] level \> 40 mIU/mL to confirm menopause). Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff. * Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception during the course of the study and for the following durations after the last dose of treatment (whichever is later). An additional contraceptive method, such as a barrier method (eg, condom), is required. In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. * Through 7 days after the last dose of casdatifan and 120 days after the last dose of zimberelimab for women of childbearing potential and for men * Ability to understand and the willingness to sign a written informed consent document. * Ability to swallow tablets. Exclusion Criteria: * Any prior systemic therapy for treatment of renal cell carcinoma. * Any radiation therapy within 4 weeks before the first dose of study treatment. * Any clear evidence of distant metastases. Enlarged lymph nodes that are planned to be removed during nephrectomy are permitted. * Clinical pneumonitis or concern for inflammatory lung disease at time of screening. * Any complementary medications (eg, herbal supplements or traditional Chinese medicines) with the intention to treat the disease under study within 2 weeks before first dose of study treatment. * Other prior malignancy active within the previous year except for locally curable cancers (\>90%) that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or Gleason 6 prostate cancer. Also, indolent malignancies, including but not limited to early-stage chronic lymphocytic leukemia and follicular lymphoma, that don't require anti-cancer treatment, could be allowed after discussion with the medical monitor. * QTc ≥ 480 msec using Fridericia's correction (QTcF) (based on an average of triplicate recordings). * Malabsorption condition that would alter the absorption of orally administered medications. * Patient has had any major cardiovascular event within 6 months prior to study drug administration including but not limited to myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic event, pulmonary embolism, clinically significant ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes) or New York Heart Association Class III or IV heart failure. * The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: a. Cardiovascular disord