Prospective, Open-label, Multi-cohort Study of Becotatug Vedotin With Tislelizumab and Chemotherapy in Esophageal Squamous Cell Carcinoma - Phase 2

Inclusion criteria

• Age ≥ 18 years.
• Male or non-pregnant, non-lactating female.
• ECOG performance status of 0 or 1, with no deterioration within 7 days.
• Histologically confirmed locally advanced or metastatic esophageal squamous cell carcinoma.
• No prior systemic therapy for ESCC. Patients who have received neoadjuvant or adjuvant therapy must have experienced disease progression or recurrence more than 6 months after completion of that treatment.
• Patients with metastatic disease must have at least one measurable lesion per RECIST 1.1 criteria; patients with disease after neoadjuvant therapy must have an evaluable lesion.
• Adequate organ and bone marrow function, as demonstrated by the following laboratory values:

• Hemoglobin (HGB) ≥ 90 g/L.
• Absolute neutrophil count (NEUT) ≥ 1.5 × 10⁹/L.
• Platelet count (PLT) ≥ 80 × 10⁹/L.
• Total bilirubin (TBIL) ≤ 1.5 × the upper limit of normal (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; for patients with liver metastases, ALT and AST ≤ 5 × ULN.
• Creatinine clearance ≥ 50 mL/min (calculated by the Cockcroft-Gault formula).
• Urine protein < (++) or 24-hour urinary protein < 1.0 g.
• Normal coagulation function and no active bleeding:

• International Normalized Ratio (INR) ≤ 1.5.
• Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN.
• For women of childbearing potential: negative pregnancy test (serum or urine) within 14 days prior to enrollment, and agreement to use adequate contraception during the study period and for 8 weeks after the last dose of study drug. For men: surgically sterile or agreement to use adequate contraception during the study period and for 8 weeks after the last dose of study drug.
• Expected survival ≥ 6 months.
• Patient voluntarily participates in the study and signs the informed consent form (ICF).
• Patient is expected to be compliant and able to undergo follow-up for efficacy and adverse events as required by the protocol.

Exclusion criteria

Patients meeting any of the following criteria at screening will be excluded from the study:

• Prior treatment with any anti-EGFR monoclonal antibody, or with anti-PD-1/PD-L1 antibody, anti-PD-L2 antibody, anti-CD137 antibody, CTLA-4 antibody, or any other drug/antibody targeting T-cell co-stimulation or checkpoint pathways.
• Administration of a live vaccine within 4 weeks prior to enrollment or anticipated during the study period.
• Active autoimmune disease or a history of autoimmune disease within 4 weeks prior to enrollment.
• Prior allogeneic bone marrow transplantation or solid organ transplant.
• Uncontrolled hypertension at enrollment, defined as: systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 90 mmHg.
• Any disease or condition affecting drug absorption at enrollment.
• Clinically significant cardiovascular disease, including but not limited to: acute myocardial infarction within 6 months prior to enrollment; severe/unstable angina or coronary artery bypass grafting; congestive heart failure > New York Heart Association (NYHA) Class 2; ventricular arrhythmias requiring medication; left ventricular ejection fraction (LVEF) < 50%.
• Active or uncontrolled severe infection (≥ CTCAE v5.0 Grade 2 infection).
• Known HIV infection. Known clinically significant liver disease, including viral hepatitis [known hepatitis B virus (HBV) carriers must be excluded if they have active HBV infection, i.e., HBV DNA positive (>1×10⁴ copies/mL or >2000 IU/mL); known hepatitis C virus (HCV) infection with HCV RNA positive (>1×10³ copies/mL)].
• Any other disease, clinically significant metabolic abnormality, physical examination finding, or laboratory abnormality that, in the investigator's judgment, reasonably suggests the presence of a disease or condition that contraindicates the use of the investigational drug (e.g., a condition associated with seizures requiring treatment), would affect the interpretation of study results, or would place the patient at high risk.
• Patients deemed by the investigator to be unsuitable for participation in this study.