Postoperative Radiotherapy With Nimotuzumab ± Benmelstobart in Intermediate-Risk Head and Neck Squamous Cell Carcinoma

Postoperative Radiotherapy And Nimotuzumab With or Without Benmelstobart Adjuvant Therapy in Patients With Head and Neck Squamous Cell Carcinoma Having Intermediate-Risk Pathological Factors: A Multicenter Prospective Randomized Controlled Study

A multicenter, randomized, controlled, open-label, Phase II/III clinical trial designed to evaluate the efficacy and safety of postoperative radiotherapy combined with Nimotuzumab,with or without Bemcentinib, in postoperative head and neck squamouscell cancer patients with intermediate-risk pathological factor. The primary endpoint is the 3-year disease-freesurvival (DFS). A total of 193 patients will be enrolled in both the experimental and control groups, resulting in a total planned enrollment of 386 patients.

Inclusion Criteria:

• Age ≥ 18 years

• ECOG performance status: 0-2

• 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)

• Completionof curative-intent surgery, with any of the following intermediate-risk factors present postoperatively:

  ①pT3-4a;

  ②N2 disease (excluding cases with extranodal extension);

  ③Closemargin < 5 mm;

  ④Lymphovascular and/or perineural invasion;

  ⑤Invasion depth > 5mm for T2 oral cavity cancer

• Laboratory tests must meet the following criteria:

  ①Hematologic parameters (within 14 days without transfusion or blood products): a. Hemoglobin (Hb) ≥80 g/L; b.Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L; c. Platelet count (PLT) ≥ 80 × 10⁹/L;

  ②Biochemical parameters: a. Bilirubin (BIL) < 1.5 × upperlimit of normal (ULN); b.Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN;

• Expected survival time ≥ 6 months;

• Women of child bearing 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

• With PD-L1 immunohistochemistry testing

• Participant voluntarily agrees to participate in this study and signs the informed consent form

Exclusion Criteria:

• Pregnancy or lactation, or intention to become pregnant during the study period.
• Presence of active autoimmune disease or immunodeficiency, including but not limited to: myasthenia gravis, interstitial pneumonia, enteritis, autoimmune hepatitis, hypophysitis, vasculitis, nephritis, or hyperthyroidism.
• Known human immunodeficiency virus (HIV) infection, history of autoimmune diseases, or history of organ transplantation.
• 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.
• Diagnosis of another malignancy within 3 years prior to enrollment.
• 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.
• Participation in another clinical trial or completion of another clinical trial within 4 weeks prior to enrollment.
• Prior treatment of immunotherapy (including PD-1/PD-L1/CTLA-4 antibodies) or anti-EGFR agents.
• Known or suspected allergy to the investigational product or any drug related to this trial.
• Any other severe medical condition that, in the investigator's judgment, may compromise patient safety or interfere with the subject's ability to complete the study.