CELL INTELLIGENCE · 肿瘤细胞治疗研究

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.

主要终点：To evaluate the safety of CAR-T cell preparations in the treatment of CEA-positive advanced malignancies [Safety and Tolerability] · Incidence of adverse events during the study, evaluated per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) criteria · From infusion through Month 3；Obtained the recommended dose and infusion regimen of CAR-T cells for the treatment of patients with CEA-positive advanced malignancies [Safety and Tolerability] · Dose-limiting toxicity after CEA CAR-T cell infusion · From infusion through Month 3
次要终点：Assessing disease control(DCR) rates of CAR-T cell preparations in CEA-positive advanced malignancies [Effectiveness]；Objective response rate (ORR) of CEA CAR-T treatment in patients with CEA-positive advanced malignancies [Effectiveness]；Duration of Response (DOR) of CEA CAR-T treatment in patients with CEA-positive advanced malignancies [Effectiveness]；Progress-free survival(PFS) of CEA CAR-T treatment in patients with CEA-positive advanced malignancies [Effectiveness]；Overall survival(OS)of CEA CAR-T treatment in patients with CEA-positive advanced malignancies [Effectiveness]；To evaluate the efficacy of CAR-T cell preparations in CEA-positive advanced malignancies【Effectiveness】；To characterize the in-vivo cellular kinetics of CAR-T cells【pharmacokinetics】；To characterize the in-vivo cellular kinetics of CAR-T cells【pharmacokinetics】

• Intravenous of CEA-targeted CAR-T · EXPERIMENTAL · Infusion of CEA-targeted CAR-T cells by dose of 2-6x10\^5 cells/kg
• Intrapleural infusion of CEA-targeted CAR-T · EXPERIMENTAL · Infusion of CEA-targeted CAR-T cells by dose of 2-6x10\^5 cells/kg

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.