Ivonescimab Before Surgery for the Treatment of Resectable Stage II-IV Head and Neck Cancer

Inclusion Criteria: * At least 18 years of age * PD-L1 combined positive score (CPS) \>= 1 * Histologically documented advanced stage mucosal HNSCC (stage II-IV), for which surgery would be recommended in routine clinical practice * Primary tumor is amenable to fresh biopsy or availability of archival fresh frozen primary tissue * Eastern Cooperative Oncology Group (ECOG) 0-1 * Absolute neutrophil count \> 1500 cells/uL * Platelet count \>= 100,000/uL * Hemoglobin \>= 9.0 g/dL (without transfusion within 14 days prior to cycle 1, day 1) * Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) or =\< 3 x ULN for participants with Gilbert's disease * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x institutional ULN * Creatinine =\< 1.5 x institutional ULN OR estimated glomerular filtration rate (eGFR) value \>= 30/mL using the Chronic Kidney Disease Epidemiology (CKD-EPI) equation OR measured (OR calculated) creatinine clearance \>= 50 mL/min using the Cockcroft-Gault Formula * Urine protein \< 2+ or 24-hour urine protein quantification \< 1.0 g * Prothrombin time (PT) or international normalized ratio (INR) =\< 1.5 x ULN, and partial thromboplastin time (PTT) or activated (a)PTT =\< 1.5 x ULN (unless abnormalities are unrelated to coagulopathy) This applies only to patients who are not on therapeutic anti-coagulation * For patients receiving therapeutic anti-coagulation there are no coagulation parameters for eligibility. However,…