Becotatug Vedotin Plus Cisplatin and Radiotherapy in LA-ESCC

Inclusion Criteria:

* Subjects who are able to understand and voluntarily sign informed consent forms (ICFs).
* Male and female subjects at the age of ≥18 and ≤75 at the time of screening.
* Histologically confirmed esophageal squamous cell carcinoma staged as cT2-T4a, N0-N+, M0-M1 (M1 limited to supraclavicular lymph node metastasis only).
* Patients must have at least one measurable lesion as defined by RECIST version 1.1 criteria.
* Patients who have not received any prior anti-tumor treatment for esophageal cancer.
* ECOG score of 0 or 1.
* Life expectancy ≥ 3 months.
* Adequate organ function (no blood transfusion and no use of granulocyte colony-stimulating factor, or other hematopoietic stimulator support within 2 weeks before the first administration of the study drug) confirmed as evidenced by:

  1. Absolute Neutrophil Count (ANC) ≥ 1.5×10\^9/L;
  2. Hemoglobin (Hgb) ≥ 90 g/dl;
  3. Platelets (Plt) ≥ 75×10\^9/L;
  4. Bilirubin total ≤ 1.5 x ULN, or bilirubin direct \< ULN for patients with bilirubin total levels \>1.5 ULN;
  5. AST/ALT ≤ 2.5 x ULN or ≤ 5.0 x ULN if liver metastases are present;
  6. Serum creatinine \< 1.5 x ULN or creatinine clearance \> 50 mL/min (as calculated via Cockcroft-Gault formula based on the actual body weight of the subject ;
* Female subjects must not be pregnant or breastfeeding. Female or male subjects of childbearing potential must agree to practice effective contraceptive measures throughout the study period and for 6 months after completion of study treatment.

Exclusion Criteria:

* Diagnosis of any other malignancy within the past 5 years (excluding carcinoma in situ, basal cell carcinoma, etc.).
* Anyone allergic to any drug or any of its components in this regimen.
* Patients with a prior history of surgery for esophageal squamous cell carcinoma.
* Patients with a prior history of fistula caused by primary tumor infiltration.
* Patients at high risk of gastrointestinal bleeding, esophageal fistula, or esophageal perforation.
* Subjects with poor nutritional status, defined as BMI \< 18.5 kg/m² or PG-SGA score ≥ 9.
* Patients with a diagnosis of pulmonary fibrosis or interstitial pneumonia within 28 days prior to enrollment.
* Active infections such as HIV; active chronic HBV/HCV (e.g., HBV DNA ≥ 10⁴ copies/mL or ≥ 2000 IU/mL) requiring antiviral and hepatoprotective therapy before enrollment. Enrollment is allowed only when HBV DNA decreases to \< 10⁴ copies/mL or \< 2000 IU/mL, with continued antiviral therapy and regular monitoring of liver function and HBV DNA levels.
* Presence of major cardiovascular disease, including any of the following conditions:

  1. Congestive heart failure (defined as New York Heart Association \[NYHA\] Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, stent implantation, coronary artery bypass grafting, cerebrovascular accident (CVA), or hypertensive crisis within 6 months prior to enrollment.
  2. History of clinically significant ventricular arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsade de pointes).
  3. Fridericia-corrected QT interval (QTcF) \> 450 msec in males or \> 470 msec in females.
  4. History or family history of congenital long QT syndrome.
  5. Arrhythmias requiring antiarrhythmic therapy (subjects with atrial fibrillation that has been controlled for more than 30 days prior to randomization may be enrolled).
  6. History of deep vein thrombosis, pulmonary embolism, or any other serious thromboembolic event within 3 months prior to enrollment (thrombosis related to an implanted venous access port or catheter, or superficial venous thrombosis, is not considered "serious" thromboembolism).
* Severe chronic diarrhea.
* Severe psychiatric disorder.
* Use of strong inhibitors or inducers of CYP3A4, CYP2C8, and UGT1A1.
* Participation in another clinical trial within 4 weeks prior to enrollment.
* Patients who, in the opinion of the investigator, are unsuitable for participation in this study.