This prospective, single-arm, multicenter phase II trial aims to evaluate the efficacy and safety of neoadjuvant beccotatug vedotin combined with pucotenlimab and cisplatin in patients with locally advanced epidermal growth factor receptor (EGFR)-positive head and neck squamous cell carcinoma (HNSCC). A total of 40 treatment-naive patients aged 18-70 years with stage III-IV (AJCC 8th edition) EGFR-positive HNSCC will be enrolled. Participants will receive three 3-week cycles of the triple-drug regimen. Tumor response will be reassessed after cycle 3 using RECIST v1.1. Patients achieving a complete or partial response (CR/PR) may proceed to de-escalation surgery followed by definitive chemoradiotherapy, or to definitive chemoradiotherapy alone; non-responders will undergo radical surgery with or without radiotherapy/chemoradiotherapy, or definitive chemoradiotherapy, as determined by multidisciplinary team (MDT) discussion. The primary endpoint is objective response rate (ORR). Secondary endpoints include major pathological response (MPR), pathological complete response (pCR), disease control rate (DCR), 2-year progression-free survival (PFS), 2-year overall survival (OS), quality of life, and safety.
This study aims to provide preliminary evidence on the feasibility and activity of this novel triple combination in the neoadjuvant setting, potentially offering a new treatment paradigm to improve long-term outcomes and reduce recurrence.
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Single group
Becotatug Vedotin, Pucotenlimab, and Cisplatin
DrugBecotatug vedotin is an EGFR-directed antibody-drug conjugate (ADC) comprising a humanized anti-EGFR monoclonal antibody conjugated to monomethyl auristatin E (MMAE) via a cleavable valine-citrulline linker. It binds to EGFR-overexpressing tumor cells, undergoes receptor-mediated internalization, and releases MMAE to inhibit microtubule polymerization, inducing cell cycle arrest and apoptosis. Pucotenlimab is a humanized anti-PD-1 monoclonal antibody that blocks the PD-1/PD-L1 interaction, restoring T-cell-mediated antitumor immune responses. Cisplatin is a platinum-based alkylating agent that forms DNA crosslinks, leading to cell death. These three agents are administered as sequential intravenous infusions on Day 1 of each 21-day cycle: pucotenlimab 200 mg, followed by beccotatug vedotin 2.0 mg/kg, and cisplatin 60 mg/m². The regimen is given for up to 3 neoadjuvant cycles prior to definitive local therapy.
Objective response rate
Objective response rate defined as the proportion of patients achieving a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 after neoadjuvant therapy.
Major Pathological Response (MPR)
MPR is defined as the presence of ≤10% viable residual tumour cells in the surgical specimen after neoadjuvant therapy.
Pathological Complete Response (pCR)
pCR means the complete absence of invasive tumour cells in the resected primary tumour and all sampled regional lymph nodes (ypT0ypN0).
Disease Control Rate (DCR)
DCR is the proportion of patients who achieve a best overall response of complete response (CR), partial response (PR), or stable disease (SD) according to RECIST v1.1, maintained for a specified duration.
2-Year Progression-Free Survival (PFS)
PFS is the time from treatment initiation (or randomisation) until the first occurrence of disease progression (per RECIST v1.1) or death from any cause.
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Xuekui Liu
Lead sponsor
Sun Yat-sen University
Sponsor institution
