A Prospective, Randomized, Phase II Study of Nimotuzumab Combined With PD-1 Inhibitors and Chemotherapy in the Treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma
This is a randomized controlled, phase II clinical study designed to explore the efficacy and safety of nimotuzumab combined with immunotherapy and chemotherapy as neoadjuvant treatment for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). The primary endpoint of the study is the 2-year event-free survival (EFS) rate. Enrollment is expected to be completed within 2 years; all patients will be followed up for at least 2 years after the last patient is enrolled.
• Age 18 to 75 years inclusive.
• Histologically or cytologically confirmed squamous cell carcinoma of the head and neck (HNSCC) (oral cavity, oropharynx, larynx, hypopharynx), stage III-IVB per AJCC 8th edition.
• Resectable disease assessed by a multidisciplinary team (MDT) including surgical, radiological, and pathological specialists.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• For oropharyngeal carcinoma: mandatory p16 immunohistochemistry (testing within standard of care is acceptable; repeat testing not required). p16 testing is not required for other tumor locations.
• Availability of tumor tissue (archived or newly obtained) for PD-L1 testing (prior testing is acceptable; repeat testing not required).
• At least one measurable lesion per RECIST 1.1.
• Life expectancy ≥ 6 months.
• Adequate hematologic function:
• White blood cell count ≥ 4.0 × 10⁹/L Absolute neutrophil count ≥ 1.5 × 10⁹/L Platelet count ≥ 100 × 10⁹/L Hemoglobin ≥ 90 g/L
⁃ Adequate renal function:
⁃ Serum creatinine ≤ 1.5 × upper limit of normal (ULN) OR
⁃ Creatinine clearance (CrCl) ≥ 60 mL/min calculated by Cockcroft-Gault formula:
⁃ Female: CrCl (mL/min) = (140 - age) × body weight (kg) × 0.85 / (72 × serum creatinine (mg/dL)) Male: CrCl (mL/min) = (140 - age) × body weight (kg) × 1.00 / (72 × serum creatinine (mg/dL))
⁃ Adequate hepatic function:
⁃ Total bilirubin ≤ 1.5 × ULN Aspartate aminotransferase (AST) ≤ 2.5 × ULN Alanine aminotransferase (ALT) ≤ 2.5 × ULN
⁃ Female subjects: negative pregnancy test within 2 weeks before first study drug, non-lactating.
⁃ Females: highly effective contraception required during study and for 6 months after last study drug.
⁃ Males: highly effective contraception required during study and for 6 months after last study drug.
⁃ Written informed consent obtained prior to any study-specific procedures, and willingness to comply with all study visits and protocol requirements.