Ivonescimab Plus Short-Course Hypofractionated Radiotherapy as Second-Line Therapy for Esophageal Squamous Cell Carcinoma

Official title

Efficacy and Safety of Ivonescimab Combined With Short-Course Hypofractionated Radiotherapy as Second-Line Therapy for Locally Advanced/Metastatic Esophageal Squamous Cell Carcinoma: A Prospective, Single-Center, Single-Arm Phase II Clinical Study

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.

Interventions

• Drug Ivonescimab+Radiotherapy
  Short-course hypofractionated radiotherapy was administered to progressive lesions after first-line treatment, with a prescribed dose of 20 Gy in 5 fractions (95% PTV). The monoclonal antibody was initiated within 1 week after completing the radiotherapy regimen, at a dose of 20 mg/kg. Ivonescimab was administered every three weeks until disease progression, intolerable toxicity, or patient refusal.

Primary outcome measures

• PFS [Time frame: From date of enrollment until the date of first documented progression (radiologic or clinical), assessed every 8 weeks up to 36 months]
• Advese Events [Time frame: Assessed every 8 weeks up to 36 months from the date of enrollment]

Secondary outcome measures (4)

• OS [Time frame: From date of enrollment until the date of death from any cause, assessed up to 36 months]
• ORR [Time frame: From enrollment to the time of the second radiological evaluation]
• DOR [Time frame: the period from the first assessment of Complete Response (CR) or Partial Response (PR) to the first occurrence of Progressive Disease (PD) or death.]
• DCR [Time frame: From enrollment to the time of second radiological evaluation]

Eligibility criteria

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:

• 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.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Anhui Provincal Hospital — Hefei

Identifiers

NCT: NCT07188103 · 2025KY-296

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗