Becotatug Vedotin Plus Pucotenlimab and Capecitabine Followed by Concurrent Chemoradiotherapy-Immunotherapy for Locally Advanced Squamous Cell Carcinoma of the Anal Canal

This is a single-arm, exploratory clinical study intended to enroll patients with EGFR-positive Locally Advanced Squamous Cell Carcinoma of the Anal Canal (T2-4N0-1M0). Patients will first receive 2 cycles of induction therapy consisting of Becotatug Vedotin combined with Pucotenlimab and Capecitabine. Patients without disease progression upon radiological assessment will subsequently proceed to the concurrent chemoradiotherapy-immunotherapy phase, which comprises Capecitabine plus Pucotenlimab and mitomycin-C together with definitive concurrent radiotherapy. In the subsequent maintenance phase, patients will receive Pucotenlimab for a total duration of 1 year. The study aims to evaluate the efficacy and safety of Becotatug Vedotin combined with Pucotenlimab and Capecitabine, as well as the potential of this novel full-course treatment paradigm.

Inclusion Criteria: 1. Aged between 18 and 75 years, male or female; 2. Voluntarily signed the informed consent form and is willing to comply with protocol-specified requirements; 3. Histologically confirmed locally advanced anal squamous cell carcinoma of cT2-4N0-1M0 stage; 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 5. EGFR immunohistochemistry (IHC) score ≥1+ as assessed by pathological laboratory; 6. At least one measurable target lesion according to RECIST version 1.1; 7. Laboratory parameters meeting all of the following criteria: （1） Bone marrow function: haemoglobin (Hb) ≥90 g/L; white blood cell count (WBC) ≥3.0×10⁹/L; absolute neutrophil count (ANC) ≥1.5×10⁹/L; platelet count ≥100×10⁹/L; （2）Renal function: serum creatinine (Cr) ≤1.5 × upper limit of normal (ULN), and endogenous creatinine clearance (Ccr) ≥55 mL/min; （3）Liver function: total bilirubin ≤1.5 × ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN; （4）Coagulation function: international normalized ratio of prothrombin time (PT-INR) ≤1.5 × ULN, and activated partial thromboplastin time (aPTT) within the normal reference range; 8. Left-ventricular ejection fraction (LVEF) ≥50%; 9. Female subjects of child-bearing potential agree to use contraception during the study and for 6 months after study completion; have a negative serum or urine pregnancy test within 7 days prior to enrolment, and are not breastfeeding. Male subjects agree to use contraception during the study and for 6 months after study completion; 10. No participation in other investigational-drug clinical trials within 4 weeks before enrolment; 11. The subject is capable of understanding and willing to adhere to protocol-required visits, treatment, laboratory tests and other study procedures. Exclusion Criteria: 1. Diagnosis of another malignancy within the past 5 years (excluding concurrent CIN2+ or cervical cancer; in-situ carcinomas and basal-cell carcinomas outside the pelvic region are permitted). 2. Pre-existing peripheral neuropathy ≥ Grade 2 (per CTCAE Version 5.0). 3. Patients planning to undergo or having previously received organ or bone-marrow transplantation. 4. Any major surgery within 4 weeks prior to the first study treatment (diagnostic biopsy excluded). 5. Any anti-tumour therapy administered within 4 weeks prior to the first study treatment, including radiotherapy, chemotherapy, targeted therapy, immunotherapy, biologic therapy, etc. 6. Presence of uncontrolled clinical cardiac signs or diseases. 7. Active infection or fever (excluding confirmed tumour-related fever). 8. History or evidence of interstitial lung disease or active non-infectious pneumonitis. 9. Patients with other medical conditions rendering them ineligible for enrolment, such as immunodeficiency, active pulmonary tuberculosis, hepatitis B (enrolment is allowed if treated HBV-DNA \