Postoperative Radiotherapy Combined With Nimotuzumab Followed by Benmelstobart in High-Risk Patients With Head and Neck Squamous Cell Carcinoma

A Multicenter, Randomized, Controlled, Open-Label, Phase III Clinical Trial of Postoperative Radiotherapy Combined With Nimotuzumab Followed by Benmelstobart in High-Risk Patients With Head and Neck Squamous Cell Carcinoma Who Are Ineligible for Cisplatin Chemotherapy

A Multicenter, Randomized, Controlled, Open-Label, Phase III Clinical Trial.To evaluate the efficacy and safety of postoperative radiotherapy combined with Nimotuzumab followed by Benmelstobart in high-risk patients with head and neck squamous cell carcinoma who are ineligible for cisplatin chemotherapy.

The primary endpoint is disease-free survival (DFS). A total of 185 patients will be enrolled in both the study group and the control group, respectively, with a total planned enrollment of 370 patients. Enrollment is expected to be completed within 2 years, followed by a 3-year follow-up period after the last patient is enrolled.

Inclusion Criteria:

1. Age ≥ 18 years.

2. Patients ineligible for cisplatin chemotherapy, defined as meeting any of the following:① Age > 70 years;② Renal insufficiency (creatinine clearance < 50 mL/min; criterion ⑩ below does not apply if this criterion is met);③ Severe tinnitus or hearing impairment (requiring hearing aid, or audiometry showing ≥ 25 dB loss at two consecutive frequencies);④ Unable to receive intravenous hydration (e.g., due to cardiac dysfunction or other comorbidities, as judged by the investigator);⑤ Neuropathy > Grade 1;⑥ Patient refusal of chemotherapy.

3. Histologically confirmed locally advanced head and neck squamous cell carcinoma (AJCC 8th edition Stage III-IVB), including oral cavity cancer, HPV-negative/unrelated oropharyngeal cancer, hypopharyngeal cancer, and laryngeal cancer.

4. Underwent radical surgery with at least one high-risk feature:

   Extracapsular extension (ECE) of lymph node metastasis; Close margin (< 1 mm) or positive margin;

   • 4 metastatic lymph nodes, or multiple perineural invasions.

5. No evidence of distant metastasis on imaging.

6. Sufficient tumor tissue available for EGFR and PD-L1 testing; for oropharyngeal cancer, HPV/p16 testing is required (testing may be waived if results are already available).

7. Expected survival ≥ 6 months.

8. ECOG performance status 0-1.

9. Adequate hematologic function:

   WBC ≥ 3 × 10⁹/L; ANC ≥ 1.5 × 10⁹/L; Platelets ≥ 100 × 10⁹/L; Hemoglobin ≥ 90 g/L.

10. Adequate renal function:Serum creatinine ≤ 1.5 × ULN or creatinine clearance (CrCl) > 50 mL/min (calculated by Cockcroft-Gault formula):

    Female: CrCl = (140 - Age) × Weight (kg) × 0.85 / (72 × Scr (mg/dL)) Male: CrCl = (140 - Age) × Weight (kg) × 1.00 / (72 × Scr (mg/dL))

11. Adequate hepatic function:

    Total bilirubin ≤ 1.5 × ULN; AST ≤ 2.5 × ULN; ALT ≤ 2.5 × ULN.

12. Women of childbearing potential: negative serum or urine pregnancy test within 14 days before enrollment, and agreement to use effective contraception during the study.Male subjects: use effective contraception from the start of treatment until 180 days after the last study drug administration.

13. Voluntary participation in the study, signed written informed consent, good compliance, and willingness to comply with follow-up procedures.

exclusion Criteria:

1. Prior radiotherapy for head and neck cancer before enrollment.
2. Prior treatment with similar immunological or targeted agents.
3. Participation in another interventional clinical trial within 30 days prior to screening.
4. Evidence of distant metastasis.
5. History of other malignancy within the previous 5 years, except cured carcinoma in situ of the cervix, non-melanoma skin cancer, localized differentiated thyroid cancer (papillary / follicular), localized prostate cancer, and ductal carcinoma in situ.
6. Uncontrolled concurrent medical conditions (e.g., heart failure, diabetes mellitus, hypertension, thyroid disease, psychiatric disorders, etc.).
7. Known HIV infection, active viral hepatitis, or active tuberculosis.
8. Major surgical procedure within 30 days before the first dose of study medication, or planned major surgery during the study.
9. Hypersensitivity to any study drug or their components.
10. Pregnancy (confirmed by serum or urine HCG test) or lactating women; subjects of childbearing potential unwilling or unable to use effective contraception (for both male and female subjects) until at least 6 months after the last study treatment.
11. Subjects considered inappropriate for study participation by the investigator.
12. Subjects unwilling to participate in the study or unable to provide written informed consent.