Becotatug Vedotin Plus Pucotenlimab and Platinum Chemotherapy in Locally Advanced Epidermal Growth Factor Receptor (EGFR)-Positive Head and Neck Squamous Cell Carcinoma

NCT07814287 | Recruiting Phase 2 DMC

• 1 other identifier: SL-B2026-102-02
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Head and Neck Squamous Cell Carcinoma, HNSCC

Keywords

antibody-drug conjugate; Head and neck squamous cell carcinoma, HNSCC; Neoadjuvant combination therapy

Outcome Measures

Primary Outcomes (1)

• 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.

  After 3 cycles of neoadjuvant therapy (approximately 9 weeks)

Secondary Outcomes (8)

• Major Pathological Response (MPR)

  At the completion of definitive surgery

• Pathological Complete Response (pCR)

  At the completion of definitive surgery

• Disease Control Rate (DCR)

  After 3 cycles of neoadjuvant therapy (approximately 9 weeks)

• 2-Year Progression-Free Survival (PFS)

  Up to 2 years

• 2-Year Overall Survival (OS)

  Up to 2 years

Study Arms (1)

Neoadjuvant Beccotatug Vedotin + Pucotenlimab + Cisplatin for Locally Advanced EGFR-positive HNSCC

EXPERIMENTAL

Participants receive 3 cycles of neoadjuvant combination therapy on a 21-day (Q3W) cycle. On Day 1 of each cycle, pucotenlimab 200 mg is administered intravenously over 60 ± 15 minutes, followed at least 30 minutes later by beccotatug vedotin 2.0 mg/kg intravenously over 60 ± 10 minutes, and cisplatin 60 mg/m² intravenously on the same day. All drugs are given at full doses (permissible ±10% variance) with protocol-defined dose modifications for toxicity per NCI-CTCAE v5.0. After completing 3 cycles, tumor response is reassessed per RECIST v1.1. Responders (CR/PR) may proceed to de-escalation surgery plus definitive chemoradiotherapy or definitive chemoradiotherapy alone, while non-responders undergo radical surgery with or without radiotherapy/chemoradiotherapy or definitive chemoradiotherapy alone based on multidisciplinary team evaluation. Beccotatug vedotin and pucotenlimab are not administered during the subsequent concurrent chemoradiotherapy phase.

Drug: Becotatug Vedotin, Pucotenlimab, and Cisplatin

Interventions

Becotatug Vedotin, Pucotenlimab, and Cisplatin DRUG

Becotatug 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.

Neoadjuvant Beccotatug Vedotin + Pucotenlimab + Cisplatin for Locally Advanced EGFR-positive HNSCC

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically and/or cytologically confirmed, previously untreated (excluding diagnostic procedures) head and neck squamous cell carcinoma (oral cavity, oropharynx, hypopharynx, or larynx) with EGFR protein expression confirmed by immunohistochemistry (IHC), and has not received targeted therapy against the EGFR signaling pathway within 6 months prior to enrollment.
• Clinical stage T2N2-3M0 or T3-4N0-3M0 (stage III-IV) per AJCC 8th edition.
• Age 18 to 70 years.
• ECOG performance status 0 or 1.
• Assessed by head and neck oncologist as locally advanced without distant metastasis.
• At least one measurable lesion per RECIST v1.1.
• Toxicity assessment per CTCAE v4.03 (for baseline evaluation).
• Adequate organ function to tolerate surgery:
• Hematologic: WBC ≥4,000/μL, ANC ≥2,000/μL, hemoglobin ≥9 g/dL, platelets ≥100,000/μL.
• Hepatic: bilirubin ≤1.5×ULN (or ≤3×ULN if known Gilbert's syndrome), AST and ALT ≤3×ULN, alkaline phosphatase ≤3×ULN, albumin ≥3 g/dL.
• Renal: serum creatinine ≤1.5×ULN or calculated creatinine clearance ≥60 mL/min (Cockcroft-Gault).
• Willing to provide archived tumor tissue or undergo biopsy to submit at least 3 unstained FFPE sections (additional if needed) for central PD-L1 IHC testing; lesion used for biopsy cannot be a target lesion unless no other suitable lesion exists.
• Signed informed consent and willingness to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

You may not qualify if:

• History of severe hypersensitivity to any component of other monoclonal antibodies, CTLA-4, or PD-1/PD-L1 inhibitors.
• Known or suspected autoimmune disease, including dementia and seizure disorder.
• Recurrent or metastatic disease, concurrent other malignancy, or judged inoperable by head and neck surgeon.
• Coagulation abnormalities (PT \>16 s, APTT \>53 s, TT \>21 s, Fib \<1.5 g/L), bleeding tendency, or current thrombolytic/anticoagulant therapy.
• Severe cardiac or pulmonary dysfunction less than grade 3 (including grade 3).
• Laboratory values not meeting eligibility criteria within 7 days prior to enrollment.
• Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies (or any other agents targeting T-cell co-stimulation or checkpoint pathways).
• Comorbid conditions requiring chronic immunosuppressive therapy or systemic/local corticosteroids at immunosuppressive doses.
• Positive HIV; HBsAg-positive with detectable HBV DNA (≥1000 copies/mL); positive HCV antibody with detectable HCV RNA (if tested).
• Use of traditional herbal medicines with antitumor indications within 4 weeks prior to randomization.
• Active or history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, chronic diarrhea).
• Positive pregnancy test (for women of childbearing potential) or breastfeeding.
• Known active tuberculosis (TB); suspected cases require clinical evaluation to rule out.
• History of allogeneic organ or hematopoietic stem cell transplantation.
• Severe infection within 4 weeks prior to first dose, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia.

Sponsors & Collaborators

• Xuekui Liu: lead

Study Sites (2)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Central Study Contacts

Zhongyu Wang, MD

CONTACT

+86 15968705158; wangzy2@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: August 11, 2026
• First Posted: September 10, 2026
• Study Start: April 15, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: September 10, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)