Postoperative Radiotherapy With Nimotuzumab ± Benmelstobart in Intermediate-Risk Head and Neck Squamous Cell Carcinoma

Official title

Postoperative Radiotherapy And Nimotuzumab With or Without Benmelstobart Adjuvant Therapy in Patients With Head and Neck Squamous Cell Carcinoma Having Intermediate-Risk Pathological Factors: A Multicenter Prospective Randomized Controlled Study

Overview

A multicenter, randomized, controlled, open-label, Phase II/III clinical trial designed to evaluate the efficacy and safety of postoperative radiotherapy combined with Nimotuzumab,with or without Bemcentinib, in postoperative head and neck squamouscell cancer patients with intermediate-risk pathological factor. The primary endpoint is the 3-year disease-freesurvival (DFS). A total of 193 patients will be enrolled in both the experimental and control groups, resulting in a total planned enrollment of 386 patients.

Interventions

• Drug Nimotuzumab
  Nimotuzumab: 200 mg on Day 1, once weekly (QW) for a total of 6 cycles.
• Drug Nimotuzumab, Benmelstobart
  Nimotuzumab: 200 mg on Day 1, once weekly (QW) for a total of 6 cycles. Bemcentinib: 1200 mg on Day 1, every 3 weeks (Q3W) for a total of 9 cycles, initiated 3-4 weeks after completion of radiotherapy.
• Radiation Postoperative Radiotherapy
  Intensity-modulated radiation therapy (IMRT) will be administered at a total dose of 60Gy (2 Gy per fraction, 30 fractions)

Primary outcome measures

• Disease-Free Survival (DFS） [Time frame: 3-year]

Secondary outcome measures (4)

• Overall Survival (OS) [Time frame: 3-year]
• Adverse Events (AEs) [Time frame: 30 days after the last dose (approximately 8 weeks total).]
• Locoregional Recurrence-Free Survival (LRRFS) [Time frame: From enrollment until first locoregional recurrence, assessed up to 3 years after last patient enrolled]
• Distant Metastasis-Free Survival (DMFS) [Time frame: From enrollment until first distant metastasis, assessed up to 3 years after last patient enrolled]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years
• ECOG performance status: 0-2
• Histologically confirmed squamous cell carcinoma of the head and neck (oral cavity, oropharynx, larynx); oropharyngeal cancer must be p16-negative (p16 positivity defined as ≥70% staining)
• Completionof curative-intent surgery, with any of the following intermediate-risk factors present postoperatively:

①pT3-4a;

②N2 disease (excluding cases with extranodal extension);

③Closemargin < 5 mm;

④Lymphovascular and/or perineural invasion;

⑤Invasion depth > 5mm for T2 oral cavity cancer

• Laboratory tests must meet the following criteria:

①Hematologic parameters (within 14 days without transfusion or blood products): a. Hemoglobin (Hb) ≥80 g/L; b.Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L; c. Platelet count (PLT) ≥ 80 × 10⁹/L;

②Biochemical parameters: a. Bilirubin (BIL) < 1.5 × upperlimit of normal (ULN); b.Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN;

• Expected survival time ≥ 6 months;
• Women of child bearing potential must have a negative pregnancy test (serum or urine) within 7 days prior to enrollment and agree to use reliable contraception during the study period; Male subjects must use reliable contraception from before treatment initiation until 120 days after the last dose of study drug
• With PD-L1 immunohistochemistry testing
• Participant voluntarily agrees to participate in this study and signs the informed consent form

Exclusion criteria

• Pregnancy or lactation, or intention to become pregnant during the study period.
• Presence of active autoimmune disease or immunodeficiency, including but not limited to: myasthenia gravis, interstitial pneumonia, enteritis, autoimmune hepatitis, hypophysitis, vasculitis, nephritis, or hyperthyroidism.
• Known human immunodeficiency virus (HIV) infection, history of autoimmune diseases, or history of organ transplantation.
• Use of systemic immunosuppressive drugs within 2 weeks prior to initiation of study treatment, or anticipated need for systemic immunosuppressive therapy during the study treatment period.
• Diagnosis of another malignancy within 3 years prior to enrollment.
• History of Grade I or higher myocardial ischemia or myocardial infarction, severe arrhythmia, or ≥ Grade 2 congestive heart failure (New York Heart Association \[NYHA\] classification) within 6 months prior to enrollment.
• Participation in another clinical trial or completion of another clinical trial within 4 weeks prior to enrollment.
• Prior treatment of immunotherapy (including PD-1/PD-L1/CTLA-4 antibodies) or anti-EGFR agents.
• Known or suspected allergy to the investigational product or any drug related to this trial.
• Any other severe medical condition that, in the investigator's judgment, may compromise patient safety or interfere with the subject's ability to complete the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07535567 · 2026HN02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗