LA HNSCC

This is a prospective, exploratory, non-registration, multi-center clinical study to evaluate the efficacy and safety of becotatug vedotin (EGFR-ADC) combined with putlimab and radiotherapy in the perioperative treatment of locally advanced resectable head and neck squamous cell carcinoma (HNSCC). \*\*Neoadjuvant Phase\*\* (3-week cycle, 2 cycles): * Putlimab (HX008): 200 mg, Q3W, D1, IV * Becotatug vedotin (MRG003): 2.0 mg/kg, Q3W, D1, IV \*\*Adjuvant/Maintenance Phase:\*\* Surgery within 2-4 weeks post-neoadjuvant; surgical approach at investigator discretion. \*\*Group A (Postoperative pCR):\*\* * Putlimab (HX008): 200 mg, Q3W, D1, IV, up to 1 year * Adjuvant RT: 40 Gy/5 weeks \*\*Group B (Postoperative MPR):\*\* * Putlimab (HX008): 200 mg, Q3W, D1, IV, up to 1 year * Adjuvant RT: 50 Gy/5 weeks \*\*Group C (Postoperative Partial/No Response):\*\* * Low-risk (no extracapsular nodal extension \[ENE\] and negative margins): Putlimab 200 mg Q3W (up to 1 year) + RT 60 Gy/6 weeks * High-risk (ENE and/or positive margins): Putlimab 200 mg Q3W (up to 1 year) + RT 60-66 Gy/6-6.6 weeks + Cisplatin 60 mg/m², Q3W, D1, IV, for 2 cycles RT timing, field, and fractionation may be adjusted by investigators based on individual disease status. Imaging assessment every 2 cycles (±7 days) until disease recurrence, initiation of new anti-tumor therapy, withdrawal of informed consent, death, or up to 21 cycles, whichever occurs first. Additional imaging may be performed at any time if clinically indicated.

This prospective, single-arm, Phase II study aims to evaluate the efficacy, safety, and surgical conversion rate of Cetuximab combined with Tislelizumab and chemotherapy for unresectable LA HNSCC.

Neoadjuvant immunotherapy before surgery has shown good efficacy and safety in locally advanced HNSCC, particularly with the use of PD-1 inhibitors combined with chemotherapy, where some patients have achieved a high rate of pathological complete response. However, approximately 40% of patients respond poorly to neoadjuvant immunochemotherapy, with prolonged treatment courses failing to significantly improve outcomes, and some patients may even experience disease progression. For these patients, timely surgery or definitive radiotherapy combined with other well-tolerated therapeutic approaches is needed to improve pathological response rates, enhance long-term survival, and preserve organ function.