Becotatug Vedotin Plus Pucotenlimab and Platinum Chemotherapy in Locally Advanced Epidermal Growth Factor Receptor (EGFR)-Positive Head and Neck Squamous Cell Carcinoma

Inclusion Criteria: Histologically and/or cytologically confirmed, previously untreated (excluding diagnostic procedures) head and neck squamous cell carcinoma (oral cavity, oropharynx, hypopharynx, or larynx) with EGFR protein expression confirmed by immunohistochemistry (IHC), and has not received targeted therapy against the EGFR signaling pathway within 6 months prior to enrollment. Clinical stage T2N2-3M0 or T3-4N0-3M0 (stage III-IV) per AJCC 8th edition. Age 18 to 70 years. ECOG performance status 0 or 1. Assessed by head and neck oncologist as locally advanced without distant metastasis. At least one measurable lesion per RECIST v1.1. Toxicity assessment per CTCAE v4.03 (for baseline evaluation). Adequate organ function to tolerate surgery: Hematologic: WBC ≥4,000/μL, ANC ≥2,000/μL, hemoglobin ≥9 g/dL, platelets ≥100,000/μL. Hepatic: bilirubin ≤1.5×ULN (or ≤3×ULN if known Gilbert's syndrome), AST and ALT ≤3×ULN, alkaline phosphatase ≤3×ULN, albumin ≥3 g/dL. Renal: serum creatinine ≤1.5×ULN or calculated creatinine clearance ≥60 mL/min (Cockcroft-Gault). Willing to provide archived tumor tissue or undergo biopsy to submit at least 3 unstained FFPE sections (additional if needed) for central PD-L1 IHC testing; lesion used for biopsy cannot be a target lesion unless no other suitable lesion exists. Signed informed consent and willingness to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. Exclusion Criteria: History of severe hypersensitivity to any component of other monoclonal antibodies, CTLA-4, or PD-1/PD-L1 inhibitors. Known or suspected autoimmune disease, including dementia and seizure disorder. Recurrent or metastatic disease, concurrent other malignancy, or judged inoperable by head and neck surgeon. Coagulation abnormalities (PT \>16 s, APTT \>53 s, TT \>21 s, Fib \<1.5 g/L), bleeding tendency, or current thrombolytic/anticoagulant therapy. Severe cardiac or pulmonary dysfunction less than grade 3 (including grade 3). Laboratory values not meeting eligibility criteria within 7 days prior to enrollment. Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies (or any other agents targeting T-cell co-stimulation or checkpoint pathways). Comorbid conditions requiring chronic immunosuppressive therapy or systemic/local corticosteroids at immunosuppressive doses. Positive HIV; HBsAg-positive with detectable HBV DNA (≥1000 copies/mL); positive HCV antibody with detectable HCV RNA (if tested). Use of traditional herbal medicines with antitumor indications within 4 weeks prior to randomization. Active or history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, chronic diarrhea). Positive pregnancy test (for women of childbearing potential) or breastfeeding. Known active tuberculosis (TB); suspected cases require clinical evaluation to rule out. History of allogeneic organ or hematopoietic stem cell transplantation. Severe infection within 4 weeks prior to first dose, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia. Planned major surgery within 30 days after first dose (or not fully recovered from prior surgery), except for minor procedures (e.g., port placement, biopsy) if performed at least 24 hours before first dose.