A Study of CEA-Targeted CAR-T Therapy in Patients With CEA-Positive Advanced Solid Tumors

A Clinical Study to Evaluate the Safety and Efficacy of CEA-Targeted Chimeric Antigen Receptor T (CAR-T) Cells in Patients With CEA-Positive Advanced Malignant Solid Tumors

This study is a single-arm, open-label, dose-escalating + dose-expansion clinical study, aiming to evaluate the safety and efficacy of CEA-targeted CAR-T cell preparations, and to preliminarily observe the study drug in CEA-positive advanced malignant tumors. The pharmacokinetic characteristics of CAR-T cell preparations for the treatment of patients with CEA-positive advanced malignancies were obtained and the recommended dose and infusion schedule.

According to the different infusion methods, patients will be assigned to two parallel subgroups: intravenous infusion, intrapleural infusion.

Within each subgroup, the study is conducted in two sequential parts:

1. .Part A (dose-escalation): escalation begins at the lowest dose level; 3-6 subjects are enrolled at each dose level;
2. .Part B (dose-expansion): additional subjects are treated at the recommended dose identified in Part A to further evaluate safety and preliminary efficacy.

Inclusion Criteria:

1. Aged 18 years or older, of any gender.

2. Histologically or cytologically confirmed advanced, metastatic, or recurrent solid tumors, including non-small cell lung cancer and breast cancer.

3. Disease progression or intolerance after at least second-line standard therapy, including but not limited to surgery, chemotherapy, radiotherapy, targeted therapy, or immunotherapy.

4. CEA positivity confirmed by immunohistochemistry (IHC) in tumor samples within 3 months of screening (clear membrane staining, with positivity rate ≥10%). If the IHC result is more than 3 months old, serum CEA must be above 10 ng/mL.

5. At least one evaluable lesion according to RECIST 1.1, with a longest diameter of ≥10 mm for non-lymph node lesions and a shortest diameter of ≥15 mm for lymph node lesions. Malignant pleural effusion is acceptable for the chest infusion subgroup.

6. For patients with malignant pleural effusion, accurate volume assessment of pleural effusion by imaging (CT or MRI) and cytological or thoracoscopic biopsy confirmation of malignant pleural effusion.

7. ECOG performance status of 0-2.

8. Life expectancy of 12 weeks or more.

9. No serious psychiatric disorders.

10. The following organ function criteria should be met unless otherwise specified:

    1. Hematology: White blood cell count >2.0×10^9/L, neutrophils >1.0×10^9/L, lymphocytes >0.5×10^9/L, platelets >50×10^9/L, hemoglobin >80 g/L.
    2. Cardiac function: Echocardiography showing ejection fraction ≥50%, with no significant abnormalities on ECG.
    3. Renal function: Serum creatinine ≤2.0×ULN.
    4. Liver function: ALT and AST ≤3.0×ULN (≤5.0×ULN for those with liver tumor infiltration).
    5. Total bilirubin ≤2.0×ULN.
    6. Oxygen saturation >92% without supplemental oxygen.

11. Eligible for single or venous blood collection with no contraindications to cell collection.

12. Consent to use a reliable and effective method of contraception for 1 year after CAR-T cell infusion (excluding the rhythm method).

13. The participant or their authorized guardian agrees to participate in the clinical trial and signs the informed consent form (ICF), indicating an understanding of the trial's purpose and procedures.

Exclusion Criteria:

1. Clinical symptoms of CNS metastasis or meningeal metastasis at screening, or other evidence suggesting that CNS metastasis or meningeal metastasis is uncontrolled, as determined by the investigator.

2. Participation in other clinical trials within 4 weeks prior to screening.

3. Receipt of a live attenuated vaccine within 4 weeks prior to screening.

4. Receipt of chemotherapy, targeted therapy, or other experimental drugs within 14 days or at least 5 half-lives (whichever is shorter) prior to screening.

5. Active or uncontrolled infection requiring systemic treatment.

6. Tumor compression of the trachea or major blood vessels, with significant risk as assessed by the investigator.

7. History of any of the following cardiac diseases:

   1. New York Heart Association (NYHA) Class III or IV congestive heart failure.
   2. Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months prior to screening.
   3. Clinically significant ventricular arrhythmias or unexplained syncope (except those caused by vasovagal or dehydration).
   4. History of severe non-ischemic cardiomyopathy.

8. Active autoimmune disease or other conditions requiring long-term immunosuppressive therapy.

9. History of or concurrent untreated malignancies within 3 years, except for basal cell carcinoma or in situ cervical cancer.

10. Positive for HBsAg or HBcAb with HBV DNA levels above the normal range, HCV antibody positive with HCV RNA levels above the normal range, HIV antibody positive, or positive for syphilis.

11. Pregnant or breastfeeding women.

12. Any other condition that the investigator deems unsuitable for participation in the study.