Ivonescimab with short-course hypofractionated radiotherapy for second-line esophageal squamous cell carcinoma

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

This will try Ivonescimab plus a short course of higher‑dose radiotherapy as a second‑line option for adults (18–80) with locally advanced or metastatic esophageal squamous cell carcinoma who have failed first‑line therapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 37 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Anhui Provincial Hospital (Government)
• Drugs / interventions: Ivonescimab, immunotherapy
• Locations: 1 site (Hefei, Anhui)
• Trial ID: NCT07188103 on ClinicalTrials.gov

What this trial studies

This is a prospective, single‑center, single‑arm Phase 2 study enrolling 37 patients who progressed on or were intolerant of first‑line systemic therapy. All participants will receive Ivonescimab in combination with short‑course hypofractionated radiotherapy, with no comparator group. The primary endpoints are progression‑free survival and safety; secondary endpoints include overall survival, duration of response, and objective response rate. Planned follow‑up extends across a two‑year study period to capture efficacy and adverse events.

Who should consider this trial

Good fit: Ideal candidates are adults 18–80 with histologically confirmed unresectable locally advanced, postoperative recurrent, or metastatic esophageal squamous cell carcinoma who progressed on or could not tolerate first‑line therapy, have at least one measurable lesion, and meet preset organ‑function labs.

Not a fit: Patients with non‑squamous esophageal cancer, no measurable lesions, significant organ dysfunction below the listed lab thresholds, or who cannot safely receive radiotherapy or immunotherapy are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, the combination could prolong time without disease progression and offer a new tolerable second‑line option for patients with advanced ESCC.

How similar studies have performed: Other clinical work combining immune‑based agents with radiotherapy has shown promising activity in esophageal cancer, but published data specific to ivonescimab are limited, making this approach partly exploratory.

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:

  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.

Where this trial is running

Hefei, Anhui

• Anhui Provincal Hospital — Hefei, Anhui, China (Recruiting)

Study contacts

• Study coordinator: Huiquan Liu

Conditions Esophageal Squamous Cell Carcinoma; Esophageal cancer; Hypofractionated Radiotherapy; Ivonescimab