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

NCT07188103 | Recruiting Phase 2 DMC

• 1 other identifier: 2025KY-296
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Esophageal Squamous Cell Carcinoma

Keywords

Esophageal cancer; Hypofractionated Radiotherapy; Ivonescimab

Outcome Measures

Primary Outcomes (2)

• PFS

  progression free survival

  From date of enrollment until the date of first documented progression (radiologic or clinical), assessed every 8 weeks up to 36 months

• Advese Events

  Advese Events

  Assessed every 8 weeks up to 36 months from the date of enrollment

Secondary Outcomes (4)

• 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

Study Arms (1)

Ivonescimab+Radiotherapy

EXPERIMENTAL

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.

Drug: Ivonescimab+Radiotherapy

Interventions

Ivonescimab+Radiotherapy DRUG

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.

Ivonescimab+Radiotherapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Anhui Provincial Hospital: lead

Study Sites (1)

Anhui Provincal Hospital

Hefei, Anhui, 230000, China

RECRUITING

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma; Esophageal Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Central Study Contacts

Huiquan Liu

CONTACT

+86 15005518171; 759821691@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2025
• First Posted: September 23, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: September 23, 2025

Record last verified: 2025-09

Locations

CN (1)