A Prospective, Randomized Controlled, Phase II Clinical Study of Becotatug Vedotin Combined With Pucotenlimab for Neoadjuvant and Adjuvant Treatment of Locally Recurrent Resectable Head and Neck Squamous Cell Carcinoma
This is a multicenter, randomized, controlled, Phase II clinical study designed to evaluate the efficacy and safety of neoadjuvant and adjuvant therapy with vebikotamab combined with Pucotenlimab compared to standard treatment in patients with locally recurrent resectable head and neck squamous cell carcinoma (HNSCC). Investigational Arm: The dosing regimen for the investigational arm is as follows: Pucotenlimab: 200 mg per dose, administered intravenously (IV) every 3 weeks (Q3W). No dose adjustments are permitted; however, dosing delays are allowed up to a maximum of 12 weeks from the date of the previous dose. This is administered for two preoperative cycles. Becotatug Vedotin: 2.3 mg/kg, administered IV Q3W for two preoperative cycles. Following neoadjuvant therapy, patients will undergo surgery at 4 weeks ± 7 days. Postoperatively (at 6 weeks ± 3 weeks), patients will be stratified for adjuvant therapy based on pathological response: Patients who achieve a major pathological response (MPR) and have no high-risk factors will receive 6 cycles of single-agent adjuvant Pucotenlimab (200 mg/dose, Q3W). Patients who do not achieve MPR or who present with high-risk factors will receive standard postoperative adjuvant therapy. Control Arm: Patients in the control arm will undergo upfront surgery followed by standard adjuvant therapy.
• 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.