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.
Histologically or cytologically confirmed head and neck squamous cell carcinoma (HNSCC), PD-L1 positive (CPS ≥ 1)
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)
No prior antitumor treatment (radiotherapy, chemotherapy, targeted therapy, or immunotherapy)
Age 18 to 70 years
None
Parallel
MRG003 (Becotatug vedotin) and Toripalimab
DrugToripalimab 240 mg administered intravenously over 30-60 minutes on Day 1 of each 3-week cycle, followed immediately by MRG003 (Becotatug vedotin) 2.0 mg/kg (based on actual body weight) administered intravenously without prophylactic premedication. Neoadjuvant phase: 2 cycles of both drugs. Adjuvant toripalimab: 3 cycles concurrent with radiotherapy, then 12 cycles maintenance. For MRG003 (Becotatug vedotin), monitor infusion reactions for at least 120 minutes after first dose and at least 60 minutes after subsequent doses if tolerated. Dose reduction of MRG003 (Becotatug vedotin) to 1.5 mg/kg is permitted once for toxicity; permanent discontinuation if intolerance persists at reduced dose. Toripalimab dose remains fixed throughout; no dose modification is permitted.
Toripalimab
DrugToripalimab 240 mg administered intravenously over 30-60 minutes on Day 1 of each 3-week cycle. Neoadjuvant phase: 2 cycles. Adjuvant phase (concurrent with radiotherapy): 3 cycles. Adjuvant maintenance (after radiotherapy): 12 cycles. No prophylactic premedication required. No dose modification of toripalimab is permitted.
Major Pathological Response (MPR) rate
Proportion of patients with major pathological response, defined as ≤ 10% residual viable tumor in the primary tumor and all sampled lymph nodes after completion of neoadjuvant therapy.
Event-Free Survival (EFS)
Time from randomization to first documented radiographic progression, progression leading to inoperability, or death from any cause.
Pathologic Complete Response (pCR) Rate
Proportion of subjects with no residual viable tumor cells in the primary tumor bed or resected lymph nodes after neoadjuvant therapy.
Objective Response Rate (ORR) per RECIST 1.1
Proportion of subjects achieving complete response (CR) or partial response (PR) according to RECIST 1.1 after 2 cycles of neoadjuvant therapy.
Safety: Incidence of Adverse Events and Serious Adverse Events
Incidence, severity, and relationship of adverse events (AEs) and serious adverse events (SAEs) graded by CTCAE v5.0.
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Dongguan People's Hospital
Lead sponsor
Sun Yat-Sen University Cancer Center
Collaborator
Shenzhen People's Hospital
Collaborator
Peking University Shenzhen Hospital
Collaborator
The University of Hong Kong-Shenzhen Hospital
Collaborator
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Collaborator
Huizhou Municipal Central Hospital
Collaborator
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Collaborator
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