Clinical Study of CEA Targeting Chimeric Antigen Receptor T Lymphocytes (CAR-T) for CEA Positive Advanced Lung Cancer
Lung cancer is the leading cause of morbidity and mortality in the world, of which 80%-85% are non-small cell lung cancer (NSCLC). Most patients with NSCLC are at the advanced stage of diagnosis and have a poor prognosis. The 5-year survival rate of stage III patients is about 15%, the 5-year survival rate of stage IV patients is less than 5%, and the median survival time is only 7 months. CEACAM5 (CEA), also known as CD66e, is a classic tumor marker that has been used as a marker for many types of tumors for 50 years. It is mainly expressed in lung cancer, esophageal cancer, bile duct cancer, colorectal cancer, gastric cancer and other tumor types. In previous CAR-T-related clinical trials targeting CEA, the research team found that CAR-T cell preparations had a certain killing effect on CEA positive tumor cells. At the same time, CAR-T cell preparations cannot be sustained for a long time in the body, which is also a key factor restricting the anti-tumor effect of CAR-T cells in the body. To solve this problem, the killing ability and survival ability of CAR-T cell preparations on tumor cells in vitro and in vivo were improved by optimizing CAR structure and improving culture mode.
• Age ≥18 years, regardless of gender.
• Histologically or cytologically confirmed diagnosis of advanced, metastatic, or recurrent lung cancer, including both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).
• Disease progression or intolerance following at least one line of prior therapy (including but not limited to surgery, chemotherapy, radiotherapy, targeted therapy, or immunotherapy).
• For patients with pleural effusion enrolled in the intrapleural infusion group, accurate assessment of pleural effusion volume and characteristics must be conducted via imaging (chest CT or X-ray) combined with cytological analysis. Cytological examination must confirm the presence of tumor cells in the pleural effusion, indicating malignant pleural effusion.
• Positive tumor CEA expression confirmed by immunohistochemistry (IHC) within 3 months prior to screening (defined as clear membranous staining with a positivity rate ≥10%). If IHC testing of tumor samples was performed more than 3 months prior to screening, the patient's serum CEA must be \>10 ng/mL.
• At least one measurable lesion according to RECIST 1.1 criteria: for non-nodal lesions, the longest diameter must be ≥10 mm; for nodal lesions, the short axis must be ≥15 mm.
• ECOG performance status score of 0-2.
• Expected survival of more than 12 weeks.
• No severe psychiatric disorders.
⁃ Unless otherwise specified, key organ functions must meet the following requirements:
∙ Hematologic: WBC \>2.0×10⁹/L, neutrophils \>1.0×10⁹/L, lymphocytes \>0.5×10⁹/L, platelets \>50×10⁹/L, hemoglobin \>80 g/L;
‣ Cardiac function: Left ventricular ejection fraction (LVEF) ≥50% by echocardiography, and no significant abnormalities on ECG;
‣ Renal function: Serum creatinine ≤2.0×ULN;
‣ Hepatic function: ALT and AST ≤3.0×ULN (≤5.0×ULN if liver metastases are present);
‣ Total bilirubin ≤2.0×ULN;
‣ Oxygen saturation (SpO₂) \>92% on room air.
⁃ Eligible for leukapheresis or peripheral venous blood collection and without contraindications for cell collection.
⁃ Subjects must agree to use reliable and effective contraception (excluding rhythm method) from the time of informed consent until 1 year after CAR-T cell infusion.
⁃ Subject or legally authorized representative must voluntarily sign the informed consent form (ICF), indicating understanding of the study objectives and procedures and willingness to participate in the clinical trial.