• a. Patients with histologically confirmed esophageal squamous cell carcinoma (ESCC) , aged 18-80 years;

• b. Unresectable locally advanced, postoperative recurrent, or metastatic ESCC that has progressed on or is intolerant to first-line systemic therapy. For patients who received definitive concurrent chemoradiotherapy (CCRT) , disease progression during or within 6 months post-treatment is considered first-line treatment failure;

• c. At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) . All positive regional lymph nodes are counted as a single lesion, while non-regional metastatic lymph nodes are counted per station;

• d. Adequate major organ function, defined as:

‣ Hematology:

• Hemoglobin (Hb) ≥ 90 g/L

∙ White blood cell (WBC) count ≥ 1.5 × 10⁹/L

∙ Platelet count ≥ 60 × 10⁹/L

⁃ Serum biochemistry:

• Albumin ≥ 25 g/L

∙ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN)

∙ Total bilirubin ≤ 1.5 × ULN

∙ Serum creatinine ≤ 1.5 × ULN or creatinine clearance (CrCl) ≥ 60 mL/min

⁃ Echocardiography:

⁃ Left ventricular ejection fraction (LVEF) ≥ 50% (lower limit of normal)

• e. Eastern Cooperative Oncology Group (ECOG) performance status: 0-2;

• f. Expected survival ≥ 3 months;

• g. Voluntarily enrolled, with signed informed consent, and willing to comply with study protocols and follow-up.