Vebrekotuzumab ± Anti-PD-1 in Pretreated Advanced ESCC

Inclusion Criteria

• •1. Willing to voluntarily sign the informed consent form and comply with the protocol requirements.
• •2. Age ≥18 years on the day of signing the informed consent form, regardless of gender.
• •3. Life expectancy ≥12 weeks.
• •4. Patients with histologically confirmed advanced recurrent or metastatic esophageal squamous cell carcinoma (ESCC) and immunohistochemistry (IHC) confirmed positive epidermal growth factor receptor (EGFR) expression (IHC 1+, 2+, or 3+).
• •5. Have experienced disease progression or intolerability after receiving at least one prior line of systemic therapy, which must have included an immune checkpoint inhibitor (e.g., anti-PD-1/PD-L1 antibody).
• •6. The patient must be able to provide a tumor tissue sample (paraffin block, paraffin-embedded sections, or fresh tissue sections) from the primary or metastatic site for pathological testing. Archived tumor tissue from the most recent treatment should be used. If archived tissue is unavailable, a new biopsy must be performed.
• •7. Must have radiographic evidence of disease progression confirmed by the investigator during or after the last treatment regimen. At baseline, there must be at least one measurable extracranial lesion per RECIST 1.1 criteria (longest diameter ≥10 mm on CT scan, or for lymph nodes, short axis ≥15 mm). The measurable lesion should not have been previously irradiated, unless it is within a prior radiation field or was previously treated locally and has documented progression.
• •8. All adverse events (AEs) from prior anti-tumor therapy have resolved to ≤ Grade 1 per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 (except for alopecia, non-clinically significant or asymptomatic laboratory abnormalities).
• •9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to the first dose.
• •10. No serious cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥50% confirmed by echocardiography or MUGA scan within 28 days prior to the first dose.
• •11. Adequate organ function within 7 days prior to the first dose, as defined by:
• •* Bone marrow: Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L; platelet count ≥100 × 10⁹/L; hemoglobin ≥90 g/L. Patient must not have received any blood transfusion or blood component therapy within 14 days prior to the first dose, nor any biologic response modifiers (e.g., G-CSF, erythropoietin) within 7 days prior to the first dose.
• •* Liver: For patients without liver metastases: total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN. For patients with liver metastases: TBIL ≤1.5 × ULN; ALT and AST ≤5 × ULN.
• •* Kidney: Serum creatinine (Cr) ≤1.5 × ULN, or calculated creatinine clearance (Cockcroft-Gault formula) ≥50 mL/min.
• •* Coagulation: International normalized ratio (INR) ≤1.5 × ULN and activated partial thromboplastin time (aPTT) ≤1.5 × ULN (unless the patient is receiving therapeutic anticoagulation).
• •12. Male patients with reproductive potential and female patients of childbearing potential must be willing to use effective contraception from signing the ICF until 6 months after the last dose of the study drug. Women of childbearing potential include premenopausal women and women within 2 years of menopause onset. A negative serum pregnancy test result must be confirmed for women of childbearing potential within ≤7 days prior to the first study drug dose.