MRG003 Plus Toripalimab Versus Toripalimab as Neoadjuvant Therapy for PD-L1-Positive, Resectable, Locally Advanced Head and Neck Squamous Cell Carcinoma

This is a multicenter, prospective, randomized, controlled Phase II trial evaluating the safety and efficacy of MRG003 (Becotatug vedotin) combined with Toripalimab versus Toripalimab alone as neoadjuvant therapy for PD-L1-positive, resectable locally advanced head and neck squamous cell carcinoma. A total of 65 subjects are planned (43 experimental, 22 control). The experimental arm receives two cycles of MRG003 (Becotatug vedotin) 2.0 mg/kg intravenously on Day 1 followed by Toripalimab 240 mg intravenously on Day 1 every 3 weeks, while the control arm receives two cycles of Toripalimab 240 mg alone. After neoadjuvant therapy, both arms undergo radical surgery 3-4 weeks later, followed by risk-adapted adjuvant radiotherapy or chemoradiotherapy with concurrent Toripalimab (3 cycles) and then 12 cycles of adjuvant Toripalimab maintenance. The primary endpoint is the major pathological response rate.

1. Histologically or cytologically confirmed head and neck squamous cell carcinoma (HNSCC), PD-L1 positive (CPS ≥ 1) 2. Treatment-naïve, pathologically confirmed stage III-IVA resectable non-oropharyngeal HNSCC (oral cavity, larynx, hypopharynx) OR HPV-negative oropharyngeal SCC, OR HPV-positive stage III T4N0-2 resectable oropharyngeal cancer (AJCC 8th edition) 3. No prior antitumor treatment (radiotherapy, chemotherapy, targeted therapy, or immunotherapy) 4. Age 18 to 70 years 5. ECOG performance status 0 or 1 6. Adequate organ function within 14 days before first dose (no blood products or growth factors within 14 days): * ANC ≥ 1.0 × 10⁹/L, Hb ≥ 90 g/L, PLT ≥ 75 × 10⁹/L * ALT/AST ≤ 1.5 × ULN, total bilirubin ≤ 1.5 × ULN, ALP \< 2.5 × ULN * CrCl ≥ 50 mL/min (Cockcroft-Gault) * APTT and INR ≤ 1.5 × ULN 7. At least one measurable lesion per RECIST 1.1 8. Life expectancy ≥ 12 weeks 9. Female subjects of childbearing potential and male subjects with reproductive potential must use medically accepted contraception during treatment and for 3 months after last dose 10. Voluntary signed informed consent, good compliance, willing to undergo follow-up