Clinical Study of Combined EphA2-targeted CAR-DC and CAR-T Cell Therapy for Non-small Cell Lung Cancer
This is an open-label, single-arm clinical study designed to evaluate the safety and preliminary efficacy of EphA2-targeted CAR-DC combined with CAR-T cell therapy in patients with non-small cell lung cancer.
• Pathologically confirmed stage IV non-small cell lung cancer (NSCLC) with at least one measurable lesion according to RECIST 1.1 criteria (i.e., a lesion with the longest diameter ≥10 mm on spiral CT scan or a lymph node with a short axis ≥15 mm).
• Tumor tissue tested positive for EphA2 expression by immunohistochemistry (≥20%).
• Disease progression after standard treatment or no available standard treatment (patients must have received at least two prior systemic therapies, including but not limited to chemotherapy and immune checkpoint inhibitors; patients with actionable driver mutations must have failed targeted therapy).
• ECOG performance status: 0-1.
• Expected survival ≥6 months.
• Toxicities related to prior anti-tumor treatments must have resolved to baseline levels or ≤ Grade 1 (excluding residual alopecia); Grade ≤2 neurotoxicity is acceptable. Washout periods: 4 weeks for chemotherapy and immunotherapy, 2 weeks for targeted therapy.
• Adequate organ function, including:
‣ Adequate hematologic function: Absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelet count ≥75×10\^9/L, hemoglobin ≥9 g/dL. No transfusions, granulocyte colony-stimulating factor (G-CSF), thrombopoietin, or erythropoietin allowed within 14 days before blood tests.
⁃ Adequate hepatic function: Total bilirubin (TBIL) \<1.5× upper limit of normal (ULN); AST and ALT \<2.5×ULN. For patients with Gilbert's syndrome, TBIL \<2×ULN; if liver metastases are present, AST and ALT \<5×ULN.
⁃ Adequate renal function: Serum creatinine (Cr) ≤1.5×ULN, or if Cr \>1.5×ULN, creatinine clearance (CrCl) ≥60 mL/min calculated using the Cockcroft-Gault formula.
⁃ Adequate coagulation function: Prothrombin time (PT) and activated partial thromboplastin time (APTT) \<1.5×ULN; international normalized ratio (INR) \<1.5 or within the target range if on anticoagulant therapy.
• Subjects of reproductive potential must be willing to use effective contraception.
• Ability to understand and voluntarily sign the informed consent form.
⁃ Willingness to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.