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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- PFS
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Ivonescimab+Radiotherapy (Drug)
结局指标
主要结局
PFS
时间窗: From date of enrollment until the date of first documented progression (radiologic or clinical), assessed every 8 weeks up to 36 months
progression free survival
Advese Events
时间窗: Assessed every 8 weeks up to 36 months from the date of enrollment
Advese Events
次要结局
- OS(From date of enrollment until the date of death from any cause, assessed up to 36 months)
- ORR(From enrollment to the time of the second radiological evaluation)
- DOR(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(From enrollment to the time of second radiological evaluation)