Becotatug Vedotin Plus Pucotenlimab in Locally Advanced Head and Neck Squamous Cell Carcinoma With Suboptimal Response to Induction Immunochemotherapy

Trial details

Who runs it

Sun Yat-sen University

Trial code

NCT07915258

Record updated

2026. november 4.

Original description

Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) may receive chemotherapy combined with immunotherapy before surgery to reduce tumor size. However, some patients do not respond adequately to this initial treatment, and additional treatment options are needed.Read full original descriptionShow less

A Prospective, Multicenter, Single-Arm, Phase II Clinical Study of Becotatug Vedotin Combined With Pucotenlimab in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma With Suboptimal Response to Induction Immunochemotherapy

Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) may receive chemotherapy combined with immunotherapy before surgery to reduce tumor size. However, some patients do not respond adequately to this initial treatment, and additional treatment options are needed.

This study aims to evaluate the effectiveness and safety of combining becotatug vedotin (MRG003), an antibody-drug conjugate that targets the epidermal growth factor receptor (EGFR), with pucotenlimab (HX008), a PD-1 immune checkpoint inhibitor, in patients whose disease remains stable or progresses after induction immunotherapy combined with platinum-based chemotherapy.

This is a prospective, multicenter, single-arm, phase II clinical trial. Eligible patients with locally advanced, resectable HNSCC will receive two cycles of becotatug vedotin plus pucotenlimab, administered every three weeks before surgery. After treatment, patients will undergo tumor response assessment followed by curative-intent surgery and appropriate postoperative treatment.

The primary objective is to evaluate the objective response rate (ORR), defined as the proportion of patients achieving complete or partial tumor response. The study will also assess pathological response, surgical outcomes, treatment safety, and long-term survival.

The study seeks to determine whether this additional preoperative treatment strategy may improve tumor response and provide further opportunities for organ preservation in patients who have not benefited adequately from initial induction immunochemotherapy.

**Inclusion Criteria:**; Voluntarily provides written informed consent before undergoing any study-specific procedures; Aged 18 to 70 years, regardless of sex; Histologically confirmed locally advanced (stage III-IVA, AJCC 8th edition) head and neck squamous cell carcinoma (HNSCC); Has received at least two cycles of induction immunochemotherapy comprising platinum-based chemotherapy and a PD-1 inhibitor; Has achieved stable disease (SD) or progressive disease (PD) as the best response to induction immunochemotherapy according to RECIST v1.1. A multidisciplinary team (MDT) considers that additional adaptive neoadjuvant therapy may reduce tumor burden, decrease the extent of surgical resection, or improve the opportunity for organ preservation; The interval between completion of induction immunochemotherapy and the first dose of study treatment does not exceed 28 days; Disease remains amenable to curative-intent surgery with an anticipated R0 resection, as confirmed by an MDT including an experienced head and neck surgeon; Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; At least one measurable lesion according to RECIST v1.1 before initiation of study treatment; Adequate organ function, as assessed within 7 days before the first study dose:; Absolute neutrophil count ≥1.5 × 10⁹/L; Platelet count ≥100 × 10⁹/L; Hemoglobin ≥90 g/L; Total bilirubin ≤1.5 × upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN (≤5 × ULN in the presence of liver metastases); Serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min (Cockcroft-Gault formula); Women of childbearing potential and men whose partners are women of childbearing potential agree to use effective contraception throughout the study and for at least 6 months after the last dose; Willing and able to comply with study treatment, follow-up visits, laboratory examinations, and other protocol-required procedures; **Exclusion Criteria:**; Primary nasopharyngeal carcinoma; History of severe hypersensitivity to becotatug vedotin, pucotenlimab, or any of their excipients; Previous anticancer treatment for HNSCC other than the protocol-specified induction immunochemotherapy, including surgery, radiotherapy, other chemotherapy, targeted therapy, or biological therapy; Unresectable disease due to invasion of critical anatomical structures (e.g., carotid sheath involvement) or other factors, or medical contraindications to curative-intent surgery, as determined by the MDT; Distant metastatic disease (M1); Active autoimmune disease or a history of autoimmune disease requiring systemic immunosuppressive treatment within the previous 2 years, except for permitted conditions such as vitiligo or stable hypothyroidism; Active central nervous system (CNS) metastases and/or carcinomatous meningitis; Requirement for long-term immunosuppressive therapy or use of systemic corticosteroids at immunosuppressive doses (>10 mg/day prednisone or equivalent) within 7 days before the first study dose; Human immunodeficiency virus (HIV) infection; untreated active hepatitis B infection (HBsAg-positive with HBV DNA >1,000 IU/mL); or hepatitis C infection (HCV antibody-positive with detectable HCV RNA); Pregnancy or breastfeeding; Severe or uncontrolled systemic disease, including clinically significant cardiovascular, pulmonary, infectious, or endocrine disorders; Major surgery or severe trauma within 4 weeks before the first study dose; Severe bleeding tendency or coagulation disorder, or clinically significant active bleeding within 1 month before the first study dose; Any other condition that, in the investigator's opinion, may compromise participant safety, study compliance, or interpretation of study results.

ClinicalTrials.gov NCT07915258