Becotatug Vedotin plus Pucotenlimab before and after surgery for locally recurrent head and neck cancer

Inclusion Criteria:

* Age between 18 and 75 years, inclusive, regardless of sex; Histologically or cytologically confirmed locally recurrent head and neck squamous cell carcinoma (HNSCC) that is amenable to curative surgical resection. Patients must not have received any prior systemic antineoplastic therapy for the recurrent disease. (Note: Prior systemic therapy as part of a multimodality treatment for locally advanced disease is permitted, provided that ≥6 months have elapsed from the completion of such therapy to the signing of the informed consent form); Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Estimated life expectancy ≥12 weeks; At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Previously irradiated lesions may be considered measurable if disease progression has been documented at the site; Availability of tumor tissue for PD-L1 testing (paraffin-embedded specimens collected within 2 years or fresh tumor tissue);

Adequate organ function, defined as follows (assessed within 14 days prior to the first dose of the investigational product):

Bone Marrow: Absolute neutrophil count (ANC) ≥1.5×10⁹/L, platelets (PLT) ≥100×10⁹/L, hemoglobin (HB) ≥9 g/dL (no blood transfusions or blood component therapy within 14 days prior to screening); Liver \& Kidney: Serum total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (if hepatic metastasis is present, AST and ALT ≤5 × ULN are allowed). Serum creatinine ≤1.5 × ULN and calculated creatinine clearance ≥50 mL/min (using the Cockcroft-Gault formula); Coagulation: International Normalized Ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5 × ULN (applies only to patients not receiving anticoagulant therapy; patients on anticoagulants must be within the therapeutic range); Thyroid Function: Thyroid-stimulating hormone (TSH) ≤1 × ULN (if TSH is abnormal, free triiodothyronine \[FT3\] and free thyroxine \[FT4\] levels must be evaluated; enrollment is permitted if FT3 and FT4 are within normal limits); Urinary Protein: Urine dipstick protein ≤1+. If urine dipstick protein is \>1+, a 24-hour urine collection is required, and the total protein must be ≤1 g/day; Cardiac Function: Normal cardiac function, defined as a normal electrocardiogram (ECG) or ECG abnormalities with no clinical significance, and left ventricular ejection fraction (LVEF) \>50% as determined by echocardiography.

Women of childbearing potential must have a negative serum pregnancy test prior to the first dose of the investigational product; Sexually active men and women of childbearing potential must use highly effective contraception (e.g., oral contraceptives, intrauterine devices, sexual abstinence, or barrier methods combined with spermicides) throughout the entire study period and for 90 days after the end of treatment; The patient voluntarily agrees to participate in the study, signs the informed consent form, demonstrates good compliance, and agrees to cooperate with follow-up visits.

Exclusion Criteria:

* Presence of distant metastases or local lesions without surgical indications (Stage IVb or IVc); Disease progression occurring within 6 months following systemic therapy for locally advanced HNSCC; Re-irradiation to the head and neck region (including cervical, supraclavicular, and infraclavicular lymph nodes) within 6 months prior to enrollment; Prior treatment with PD-1/PD-L1/PD-L2/CTLA-4 antibodies, or agents targeting activating or inhibitory receptors on T cells (e.g., OX40, CD137); Prior treatment with antibody-drug conjugates (ADCs) bearing an MMAE payload; Participation in any other drug/treatment clinical trial within 4 weeks prior to the first dose of the investigational product, or currently participating in another trial; major surgery, unresolving adverse effects from prior surgery, live vaccines, or immunotherapy within 4 weeks prior to the first dose; radiotherapy within 2 weeks prior to the first dose; concurrent receipt of any other antineoplastic therapy; Any active autoimmune disease or history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonitis, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism). Exceptions: Vitiligo not requiring systemic therapy is permitted; childhood asthma that has completely resolved and requires no intervention in adulthood is permitted. Asthma requiring medical intervention with bronchodilators is not permitted; Current use of immunosuppressants or systemic corticosteroids for immunosuppressive purposes (at doses \>10 mg/day prednisone equivalent or equivalent efficacy) that are still being used within 2 weeks prior to enrollment; History of other malignancies within the past 5 years, except for adequately treated basal cell carcinoma of the skin, cutaneous squamous cell carcinoma, early-stage prostate cancer, and carcinoma in situ of the cervix; Active pulmonary diseases (interstitial pneumonitis, pneumonia, obstructive pulmonary disease, asthma) or a history of active pulmonary tuberculosis;

Any uncontrolled clinical conditions, including but not limited to:

Persistent or active (severe) infections; Poorly controlled hypertension (persistent blood pressure \>150/90 mmHg); Poorly controlled diabetes mellitus; Cardiac diseases (New York Heart Association \[NYHA\] Class III/IV congestive heart failure or cardiac conduction blocks); Occurrence of any of the following within 6 months prior to the first dose: deep vein thrombosis (DVT) or pulmonary embolism (PE); myocardial infarction; severe or unstable arrhythmias or angina; percutaneous coronary intervention (PCI), acute coronary syndrome (ACS), or coronary artery bypass grafting (CABG); cerebrovascular accident (CVA), transient ischemic attack (TIA), or cerebral embolism; History of psychoactive substance abuse that cannot be discontinued, or a history of psychiatric disorders; Any other severe, acute, or chronic medical condition, or laboratory abnormalities that, in the investigator's judgment, may increase the risks associated with study participation or interfere with the interpretation of study results; Poor compliance, or any other circumstances that, in the investigator's judgment, render the patient unsuitable for participation in this trial.