Overview

This is an open-label, prospective, randomized, Phase III, international multicenter clinical study to compare radiotherapy plus nimotuzumab versus radiotherapy alone in platinum-ineligible patients with locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC),

Eligibility

Inclusion Criteria:

• Eligible subjects must meet all of the following:
  • Age ≥18 years.
  • Histologically confirmed stage III-IVB (AJCC 8th edition) head and neck squamous cell carcinoma (including cancers of the oral cavity, oropharynx, hypopharynx, and larynx).
  • Unsuitable for surgical treatment (defined as: due to patient condition or tumor factors \[T3-4 N0-3 M0, or T1-2 N2-3 M0\] or medical reasons, surgery is not feasible; or an R0 resection is not achievable).
  • Suitable for definitive radiotherapy with curative intent.
  • At least one of the following reasons for being unsuitable for cisplatin-based chemotherapy:
• Age ≥65 years and, in the investigator's judgment, unable to tolerate chemotherapy;
• ECOG Performance Status \>2 (if this criterion is met, the ECOG criterion listed below may be waived);
• Renal dysfunction: creatinine clearance (CrCl) \<50 mL/min (Cockcroft-Gault) (if this criterion is met, the renal function criterion listed below may be waived);
• Severe tinnitus or hearing loss (requires a hearing aid or audiometry shows ≥25 dB loss at two consecutive frequencies);
• Peripheral neuropathy \> Grade 1;
• Inability to receive intravenous hydration (e.g., due to cardiac dysfunction) or other comorbidities, per investigator's judgment.
  • Provide tumor tissue, whenever possible, for EGFR testing; for oropharyngeal cancer, provide tissue for HPV/p16 testing if feasible (no need to retest if previously tested).
  • ECOG Performance Status 0-1 (or Karnofsky Performance Status ≥80).
  • At least one measurable lesion per RECIST 1.1.
  • Expected survival ≥6 months.
  • Adequate hematologic function: WBC ≥4×10\^9/L; absolute neutrophil count ≥1.5×10\^9/L; platelets ≥100×10\^9/L; hemoglobin ≥90 g/L.
  • Adequate renal function: serum creatinine ≤1.5×ULN or CrCl ≥60 mL/min (Cockcroft-Gault):
• Female CrCl = (140 - age) × weight (kg) × 0.85 / (72 × S\_cr \[mg/dL\])
• Male CrCl = (140 - age) × weight (kg) × 1.00 / (72 × S\_cr \[mg/dL\])
  • Adequate liver function: total bilirubin ≤1.5×ULN; AST ≤2.5×ULN; ALT ≤2.5×ULN.
  • Voluntary participation: signed written informed consent and ability to comply with visits and procedures.

Exclusion Criteria:

• Any of the following excludes enrollment:
  • Receipt of a PD-1 inhibitor, EGFR monoclonal antibody, EGFR-TKI, or anti-angiogenic agent within 4 weeks prior to enrollment.
  • Participation in another interventional clinical trial within 30 days prior to screening.
  • History of other malignancy (except cured basal cell carcinoma of the skin).
  • History of primary immunodeficiency.
  • Uncontrolled comorbid conditions (e.g., congestive heart failure, severe pulmonary disease, severe liver disease, psychiatric illness).
  • Known HIV infection, or active viral hepatitis or active tuberculosis.
  • Major surgery within 90 days before first study treatment, or planned surgery during the study.
  • Known allergy to nimotuzumab or its excipients.
  • Deemed unsuitable to participate by the investigator.
  • Unwilling or unable to sign informed consent.
  • Receipt of a live vaccine within 30 days before first dose.