In the era of immunotherapy, the standard second-line treatment regimen for locally advanced/metastatic esophageal squamous cell carcinoma (ESCC) remains controversial. This prospective, single-center, single-arm phase II clinical study aims to evaluate the efficacy and safety of Ivonescimab combined with short-course hypofractionated radiotherapy as a second-line therapy for patients with locally advanced/metastatic ESCC. The study plans to enroll 37 patients who have failed first-line treatment, without grouping, all of whom will receive Ivonescimab combined with short-course hypofractionated radiotherapy. The primary endpoints are progression-free survival (PFS) and safety, while the secondary endpoints include overall survival (OS), duration of response (DOR), and objective response rate (ORR). The study duration is 2 years.
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;
Hemoglobin (Hb) ≥ 90 g/L
a. Patients with severe organ dysfunction, uncontrolled acute infection, or significant comorbidities;
b. Patients with vertebral metastases accompanied by spinal cord compression symptoms;
c. Patients with esophagotracheal or esophagomediastinal fistulas;
d. Patients with uncontrolled pleural, pericardial, or pelvic effusions requiring repeated drainage;