Nephrectomy Clinical Trials

• Patients must have biopsy-confirmed, non-metastatic, high-risk renal cell carcinoma (RCC) with a clear cell component, defined as clinical stage T2N0, T3N0, T4N0, or any T stage with N1 disease (i.e., T2a-T4NanyM0 or TanyN1M0), and no evidence of metastatic disease

• Participants with resectable RCC are eligible, including those who have previously undergone surgical resection for RCC and subsequently developed resectable recurrent disease. Patients must be candidates for further curative-intent surgical resection. Prior systemic therapy for RCC (including VEGF-targeted therapy, immune checkpoint inhibitors, HIF-2α inhibitors, or other systemic anticancer therapies) is not allowed

• Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of botensilimab in combination with balstilimab in patients \< 18 years of age, children are excluded from this study

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (or Karnofsky ≥ 60%)

• Patients must be considered suitable for curative-intent surgical resection of RCC, including radical or partial nephrectomy, as determined by the urology team and the treating physician according to standard clinical guidelines

• Absolute neutrophil count ≥ 1,000/mcL

• Platelets ≥ 100,000/mcL

• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)

• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN

• Glomerular filtration rate (GFR) 50 mL/min (calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation)

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Also including a prior history of renal cell carcinoma

• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better

• Patients must be scheduled to undergo either partial or radical nephrectomy as part of treatment plan

• The effects of botensilimab and balstilimab on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and 4 months after completion of treatment. 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. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of botensilimab and balstilimab administration. All patients of childbearing potential must undergo a blood or urine pregnancy test within 14 days prior to receiving the first dose of botensilimab and balstilimab to confirm they are not pregnant. If dosing is delayed beyond this window, the pregnancy test must be repeated to ensure results remain current

• Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants

• Availability of pre-treatment archival slides or tissue blocks is required for inclusion in the study