Triple-drug neoadjuvant therapy for EGFR-positive locally advanced head and neck cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a multicenter, single-arm phase II study enrolling 40 treatment-naive adults aged 18-70 with stage III-IV EGFR-positive head and neck squamous cell carcinoma. Patients receive three 3-week cycles of Becotatug Vedotin plus Pucotenlimab and Cisplatin, with tumor response assessed by RECIST v1.1 after cycle 3. Responders may undergo de-escalated surgery followed by definitive chemoradiotherapy or chemoradiotherapy alone, while non-responders proceed to radical surgery or chemoradiotherapy per multidisciplinary team. The primary endpoint is objective response rate; secondary endpoints include major and pathological responses, disease control, 2-year PFS and OS, quality of life, and safety.

Why it matters

Who can join: the full rules

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Planned major surgery within 30 days after first dose (or not fully recovered from prior surgery), except for minor procedures (e.g., port placement, biopsy) if performed at least 24 hours before first dose.

Where it's running

• Sun Yat-sen University Cancer Center
  Guangzhou, Guangdong, China Recruiting
• Sun Yat-sen University Cancer Center
  Guangzhou, Guangdong, China Recruiting

Study contacts

• Study coordinator: Zhongyu Wang, MD
• Email: wangzy2@sysucc.org.cn
• Phone: +86 15968705158

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.