Ivonescimab Prior to Surgery for the Treatment of High-Risk Localized Clear Cell Renal Cell Cancer

Inclusion Criteria: * Histologic confirmation of clear cell RCC * High-risk disease defined as cT2G3-4N0M0, cT3GanyN0M0, cT4GanyN0M0, cTanyGanyN+M0 (Grade determined by biopsy) * Candidate for partial or complete nephrectomy that extirpates all tumor tissue as part of treatment plan * Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 * Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L (no blood transfusions or growth factor therapy used within 7 days of the screening complete blood count \[CBC\]) * Platelet count ≥ 100 × 10\^9/L (no blood transfusions or growth factor therapy used within 7 days of the screening CBC) * Hemoglobin ≥ 9.0 g/dL (no blood transfusions or growth factor therapy used within 7 days of the screening CBC) * Creatinine clearance (CrCL) ≥ 50 mL/min using the Cockcroft-Gault formula or estimated glomerular filtration rate (eGFR) value ≥ 60 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (adjustment by body surface area \[BSA\] is not required for eGFR) * Urine protein \< 2+ or 24-hour urine protein quantification \< 1.0 g * Serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); For patients with liver metastases or confirmed/suspected Gilbert syndrome, TBIL ≤ 3 × ULN * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; For patients with liver metastases, AST and ALT ≤ 5 × ULN * Coagulation: Prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 × ULN, and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy). This applies only to patients who are not on therapeutic anti-coagulation. Patients receiving therapeutic anti-coagulation should be on a stable dose * Female patients of childbearing age must have negative serum pregnancy test results before enrollment or per region-specific guidance documented in the informed consent and a negative urine pregnancy test on the day of first dose prior to dosing * Female patient of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 90 days after the last dose of the ivonescimab * Unsterilized male patients having sex with a female partner of childbearing potential, or a pregnant or breastfeeding partner must agree to use barrier contraception (male condom) for the duration of the treatment period until 90 days after the last dose of ivonescimab. Male patients with female partners of childbearing potential must have the female partner agree to use at least 1 form of highly effective contraception for the duration of the treatment period until 90 days after the last dose of ivonescimab * Adults aged 18 years or older Exclusion Criteria: * Prior systemic anti-tumor treatment for RCC * Major surgical procedures or serious trauma within 4 weeks prior to enrollment, or plans for major surgical procedures within 4 weeks after the first dose (as determined by the investigator). Minor local procedures (excluding central venous catheterization and port implantation) within 3 days prior to enrollment * History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to enrollment, including but not limited to: * Current use of prophylactic or full-dose anticoagulants or anti-platelet agents for therapeutic purposes that is not stable prior to enrollment is not allowed. The use of full-dose anticoagulants is permitted as long as the international normalized ratio (INR) or activated partial thromboplastin time (aPTT) is within therapeutic limits according to the medical standard of the enrolling institution * Poorly controlled hypertension with repeated systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy * Active autoimmune or lung disease requiring systemic therapy (eg, with disease modifying drugs, prednisone \> 10 mg daily or equivalent, immunosuppressant therapy) within 2 years prior to enrollment, however the following will be allowed: * Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted * Intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections is permitted * History of major diseases before enrollment, specifically: * Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association \[NYHA\] classification ≥ grade 2) or unstable vascular disease (eg, aortic aneurysm at risk of rupture, Moyamoya disease) that required hospitalization within 12 months prior to enrollment, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia) * History of esophageal gastric varices, severe ulcers, wounds that do not heal, abdominal fistula, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6 months before enrollment * History of any grade arterial thromboembolic event, Grade 3 and above venous thromboembolic event, as specified in National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 12 months prior to enrollment * Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks before enrollment * History of perforation of the gastrointestinal tract and/or fistula, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection) within 6 months prior to enrollment * Imaging during the screening period shows that the patient has metastatic disease * Symptomatic central nervous system (CNS) metastases, CNS metastases with hemorrhagic features, CNS metastasis ≥ 1.5 cm, CNS radiation within 7 days prior to enrolment, potential need for CNS radiation within the first cycle, or leptomeningeal disease * Live vaccine or live attenuated vaccine within 4 weeks prior to planned enrolment, or if scheduled to receive a live vaccine or live attenuated vaccine during the study period. Inactivated vaccines are permitted * Severe infection within 4 weeks prior to enrolment, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia; active infection (as determined by the investigator) requiring systemic anti-infective therapy within 2 weeks prior to enrolment (excluding antiviral therapy for hepatitis B or C) * Has pre-existing peripheral neuropathy that is ≥ Grade 2 by CTCAE version 5 * Uncontrolled pleural effusions, pericardial effusions, or ascites that is clinically symptomatic * History of non-infectious pneumonia requiring systemic corticosteroids, or current interstitial lung disease * Active or prior history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea) * Known history of human immunodeficiency virus (HIV) whose viral load is not controlled * Current use of systemic corticosteroids (\> 10 mg daily prednisone or equivalent) * Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation * Patients with active hepatitis B are required to have stable or declining levels of hepatitis B DNA by polymerase chain reaction (PCR) on appropriate anti-viral therapy with acceptable tolerability for one month prior to enrolment. All patients with active hepatitis C (hepatitis C virus \[HCV\] antibody positive with HCV ribonucleic acid \[RNA\] levels above the lower limit of detection) are excluded * Known allergy to any component of any study drug; known history of severe hypersensitivity to other monoclonal antibodies * History or current evidence of any condition (medical \[including adverse events from prior anticancer therapy, disorders secondary to tumor\], surgical or psychiatric \[including substance abuse\]), or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, might lead to higher medical risk and/or is not in the best interest of the patient to participate, in the opinion of the treating investigator * Patient is breastfeeding or plans to breastfeed during the study * History of severe immune-mediated adverse events from immunotherapy agents (i.e. PD1/PDL1/CTLA4 inhibitors), or immune-related ocular toxicity, pneumonitis, or cardiomyopathy of any grade