Becotatug Vedotin Combined With Pucotenlimab as Neoadjuvant Therapy for Resectable Recurrent Head and Neck Squamous Cell Carcinoma After Progression on Immunotherapy: A Prospective Phase II Study

Prior treatment

• Comorbidities requiring long-term immunosuppressive therapy or corticosteroids at immunosuppressive doses
• High-dose systemic corticosteroids within 4 weeks prior to enrollment
• Concurrent participation in other clinical trials

Other illness

• History of other malignancies (except cured basal cell carcinoma or cervical carcinoma in situ)
• Immunodeficiency or history of organ transplantation (including interstitial pneumonia, hepatitis, nephritis, hyperthyroidism, hypothyroidism)
• HIV/AIDS; untreated active hepatitis B (HBV-DNA at least 500 IU/mL); hepatitis C (HCV-RNA above detection limit); or HBV/HCV co-infection
• Significantly impaired cardiac, hepatic, pulmonary, renal, or bone marrow function
• Severe uncontrolled comorbidities or active infections
• Psychiatric disorders or mental illness resulting in lack of legal capacity

Lab values

• Laboratory values not meeting inclusion criteria within 7 days

Other

• Pregnant or lactating women; fertile patients not using effective contraception
• Refusal or inability to sign informed consent
• Other contraindications to study treatment as determined by the investigator

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Age 18-75 years at time of consent
• Histologically or cytologically confirmed recurrent head and neck squamous cell carcinoma
• Disease progression after prior treatment including both PD-1/PD-L1 inhibitor and platinum-based therapy (combined or sequential)
• EGFR protein expression positive by immunohistochemistry (IHC), with no EGFR-targeted therapy within 6 months prior to enrollment
• Willing to provide archived tumor tissue or undergo fresh tumor biopsy for EGFR testing
• At least one measurable extracranial lesion per RECIST v1.1; previously treated lesions must demonstrate clear progression 3 or more months after last local treatment
• Resectable disease with no distant metastasis, as assessed by a multidisciplinary team
• Adequate organ function within 7 days prior to enrollment: ANC at least 2.0 x 10\^9/L, platelet count at least 100 x 10\^9/L; total bilirubin less than 1.5 x ULN, ALT/AST less than 2.5 x ULN; serum creatinine less than 1.5 x ULN
• Signed informed consent prior to any study-specific procedures
• Life expectancy greater than 3 months
• Effective contraception during study and for 6 months after last dose