Ficerafusp Alfa, Pembrolizumab, and Stereotactic Body Radiotherapy (SBRT) for Head and Neck Squamous Cell Carcinoma (HNSCC)

Inclusion Criteria: * Newly diagnosed histologically or cytologically confirmed locally advanced, OPC HPV-negative head and neck squamous cell carcinoma (OPSCC) or HNSCC arising from oral cavity, larynx, or hypopharynx. * Baseline resectable disease per the judgment of the treating surgical oncologist. * Clinical stage III, IVA, or IVB disease as defined using the 8th (2017) edition of the tumor, node, metastasis (TNM) staging system by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC): * T1-2, N1-3 or * T3, any N or * T4, any N * Documented tumor PD-L1 CPS ≥ 1 (by PD-L1 IHC pharmDx assay), determined locally. * Willing to provide blood and newly obtained core or excisional biopsy of tumor lesion pre-treatment and at the time of surgery for pathologic and correlative analyses. * Age 18 years or older at the time of informed consent. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Adequate organ and marrow function as defined below: * Absolute neutrophil count ≥ 1.5 K/cumm * Platelets ≥ 100 K/cumm * Hemoglobin ≥ 9 g/dL (without PRBC transfusion in the prior 7 days) * Total serum bilirubin ≤ 1.5 x IULN (except for subjects with documented diagnosis of Gilbert syndrome). For subjects with a documented diagnosis of Gilbert's syndrome, total bilirubin must be ≤ 3.0 × ULN, provided that direct bilirubin is within normal limits * AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN * Creatinine clearance (…