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.