A Phase II Study of Neoadjuvant Ivonescimab in Patients With High-Risk, Localized RCC
This phase II trial studies how well ivonescimab works prior to surgery in treating patients with high-risk clear cell kidney (renal cell) cancer that has not spread to other parts of the body (localized). Immunotherapy with monoclonal antibodies, such as ivonescimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ivonescimab may also stop or slow the cancer by blocking the growth of new blood vessels necessary for tumor growth. Giving ivonescimab before standard surgery may make the tumor smaller.
• 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