Radiotherapy with nimotuzumab versus radiotherapy alone for platinum-ineligible advanced head and neck squamous cell carcinoma

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)

This trial tests whether adding nimotuzumab to radiotherapy helps people with advanced head and neck squamous cell carcinoma who cannot receive platinum chemotherapy.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 335 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shandong Cancer Hospital and Institute (other)
• Drugs / interventions: nimotuzumab, chemotherapy
• Locations: 1 site (Shandong, Province)
• Trial ID: NCT07333274 on ClinicalTrials.gov

What this trial studies

This open-label, randomized Phase III international multicenter trial randomized platinum-ineligible adults with stage III–IVB locoregionally advanced head and neck squamous cell carcinoma to receive definitive radiotherapy with or without nimotuzumab. Radiotherapy was delivered using intensity-modulated techniques (IMRT) and nimotuzumab was given in the experimental arm. Eligible patients were those unsuitable for surgery or cisplatin-based chemotherapy because of factors such as age, poor performance status, or renal dysfunction. The study compared efficacy and safety outcomes across roughly 70 participating centers, including Shandong First Medical University Affiliated Cancer Hospital.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed stage III–IVB squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx who are unsuitable for surgical resection and ineligible for cisplatin-based chemotherapy but are suitable for definitive radiotherapy.

Not a fit: Patients with metastatic (M1) disease, non-squamous histology, those who can tolerate standard cisplatin-based chemoradiation, or those unable to receive nimotuzumab or radiotherapy are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, adding nimotuzumab to radiotherapy could improve tumor control and survival for patients who cannot receive platinum chemotherapy while avoiding systemic platinum toxicity.

How similar studies have performed: EGFR-targeting antibodies combined with radiotherapy (for example, cetuximab) have shown benefit in head and neck cancer, and smaller studies of nimotuzumab have suggested activity, but robust phase III evidence in platinum-ineligible LA-HNSCC has been limited.

Eligibility criteria

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.

Where this trial is running

Shandong, Province

• Shandong First Medical University Affiliated Cancer Hospital — Shandong, Province, China (RECRUITING)

Study contacts

• Principal investigator: Man Hu — Shandong First Medical University Affiliated Cancer Hospital
• Study coordinator: Man Hu

Conditions: Head & Neck Squamous Cell Carcinoma, Head & Neck Cancer, Nimotuzumab, Radiotherapy, locoregionally advanced head and neck squamous cell carcinoma, LA-HNSCC