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.

Inclusion Criteria:

1. Age 18 to 75 years inclusive.

2. 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.

3. Resectable disease assessed by a multidisciplinary team (MDT) including surgical, radiological, and pathological specialists.

4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

5. 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.

6. Availability of tumor tissue (archived or newly obtained) for PD-L1 testing (prior testing is acceptable; repeat testing not required).

7. At least one measurable lesion per RECIST 1.1.

8. Life expectancy ≥ 6 months.

9. 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

10. 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))

11. Adequate hepatic function:

    Total bilirubin ≤ 1.5 × ULN Aspartate aminotransferase (AST) ≤ 2.5 × ULN Alanine aminotransferase (ALT) ≤ 2.5 × ULN

12. 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.

13. Written informed consent obtained prior to any study-specific procedures, and willingness to comply with all study visits and protocol requirements.

Exclusion Criteria:

1. Received PD-1 inhibitors, EGFR monoclonal antibodies, EGFR-TKIs, or anti-angiogenic agents within 4 weeks prior to enrollment.
2. Participation in another interventional clinical trial within 30 days prior to screening.
3. In the investigator's judgment, the patient cannot tolerate or has contraindications to platinum-based chemotherapy (cisplatin or carboplatin) as specified in the protocol.
4. Unresectable disease, poor medical condition for surgery, refusal of surgery for any reason, or excessive tumor burden precluding resection.
5. History of other malignancy within the past 5 years (except cured basal cell carcinoma of the skin).
6. History of primary immunodeficiency disease.
7. Presence of uncontrolled comorbidities, including heart failure, severe pulmonary disease, severe hepatic disease, psychiatric disorders, etc.
8. Known HIV infection, active viral hepatitis, or active tuberculosis.
9. Underwent major surgery within 90 days prior to the first study drug, or planning major surgery unrelated to this cancer treatment.
10. Hypersensitivity to any study drug or their components.
11. Pregnant (confirmed by serum or urine HCG test) or lactating woman; or subject of childbearing potential unwilling or unable to use effective contraception during study treatment and for at least 6 months after the last dose of study treatment (applicable to both males and females).
12. Investigator considers the subject not suitable for study participation.
13. Unwilling to participate or unable to provide written informed consent.
14. Receipt of a live vaccine within 30 days before the first study drug administration.