Postoperative Radiotherapy With Nimotuzumab ± Benmelstobart in Intermediate-Risk Head and Neck Squamous Cell Carcinoma: A Randomized Controlled Trial

A Multicenter, Randomized, Controlled, Open-Label, Phase II/III Clinical Trial to evaluate the efficacy and safety of postoperative radiotherapy and Nimotuzumab with/without Bemcentinib in intermediate-risk pathological patients with head and neck squamous cell carcinoma.The primary endpoint is 3-year disease-free survival (DFS). A total of 193 patients will be enrolled in both the study group and the control group, respectively, with a total planned enrollment of 386 patients.

Inclusion Criteria: * 1\. Age ≥ 18 years; 2. ECOG performance status: 0-2; 3. Histologically confirmed squamous cell carcinoma of the head and neck (oral cavity, oropharynx, larynx); oropharyngeal cancer must be p16-negative (p16 positivity defined as ≥70% staining); 4. Completion of curative-intent surgery, with any of the following intermediate-risk factors present postoperatively: * pT3-4a; * N2 disease (excluding cases with extranodal extension); * Close margin \< 5 mm; * Lymphovascular and/or perineural invasion; * Invasion depth \> 5 mm for T2 oral cavity cancer; 5. Laboratory tests must meet the following criteria: 1. Hematologic parameters (within 14 days without transfusion or blood products): 1. Hemoglobin (Hb) ≥ 80 g/L; 2. Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L; 3. Platelet count (PLT) ≥ 80 × 10⁹/L; 2. Biochemical parameters: 1. Bilirubin (BIL) \< 1.5 × upper limit of normal (ULN); 2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; 6. Expected survival time ≥ 6 months; 7. Women of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days prior to enrollment and agree to use reliable contraception during the study period; male subjects must use reliable contraception from before treatment initiation until 120 days after the last dose of study drug; 8. Willingness to undergo PD L1 immunohistochemistry testing; 9. Subject voluntarily agrees to participate in this study and signs the informed consent form. Exclusion Criteria: * 1\. Pregnancy or lactation, or planning to become pregnant during the study period; 2. Presence of active autoimmune disease or immunodeficiency, including but not limited to myasthenia gravis, interstitial pneumonia, enteritis, autoimmune hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism; HIV-positive status, history of the above diseases, or history of organ transplantation; 3. Use of systemic immunosuppressive drugs within 2 weeks prior to initiation of study treatment, or anticipated need for systemic immunosuppressive therapy during the study treatment period; 4. Diagnosis of another malignancy within 3 years prior to enrollment; 5. History of Grade I or higher myocardial ischemia or myocardial infarction, severe arrhythmia, or ≥ Grade 2 congestive heart failure (New York Heart Association \[NYHA\] classification) within 6 months prior to enrollment; 6. Participation in another clinical trial or completion of another clinical trial within 4 weeks prior to enrollment; 7. Prior receipt of immunotherapy (including PD 1/PD L1/CTLA 4 antibodies) or anti EGFR agents; 8. Known or suspected allergy to the investigational product or any drug related to this trial; 9. HIV-positive status, cirrhosis, decompensated liver disease, active hepatitis, or chronic hepatitis requiring antiviral therapy; 10. Any other serious concurrent medical condition that, in the investigator's judgment, may compromise patient safety or interfere with the subject's ability to complete the study.