Overview

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.

Eligibility

Inclusion Criteria:

• 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:
  1. Hematology:
     1. Hemoglobin (Hb) ≥ 90 g/L
     2. White blood cell (WBC) count ≥ 1.5 × 10⁹/L
     3. Platelet count ≥ 60 × 10⁹/L
  2. Serum biochemistry:
     1. Albumin ≥ 25 g/L
     2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN)
     3. Total bilirubin ≤ 1.5 × ULN
     4. Serum creatinine ≤ 1.5 × ULN or creatinine clearance (CrCl) ≥ 60 mL/min
  3. 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.

Exclusion Criteria:

• 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;
• e. Patients with esophageal primary/metastatic lesions invading the heart or great vessels, as assessed by the responsible physician, with a risk of life-threatening hemorrhage;
• f. Patients with esophageal primary/metastatic lesions invading the trachea or bronchi, as assessed by the responsible physician, with a risk of esophagotracheal fistula;
• g. Patients not suitable for short-course hypofractionated radiotherapy, as evaluated by the responsible physician;
• h. Pregnant or lactating women;
• i. Patients with mental disorders, or those with a history of psychotropic drug abuse and unable to quit;
• j. Patients who have participated in other drug clinical trials within the past 4 weeks;
• k. Patients or their families who refuse to participate in the study.