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.
Age ≥18 years old, male or female;
Advanced, metastatic or recurrent malignant tumors diagnosed by histology or pathology, mainly colorectal cancer, esophageal cancer, gastric cancer, and pancreatic cancer;
After receiving at least second-line standard treatment failure (disease progression or intolerance, such as surgery, chemotherapy, radiotherapy, etc.) or lack of effective treatment methods;
Immunohistochemical staining of tumor samples within 3 months confirmed that the tumor was CEA positive (clear membrane staining, positive rate ≥ 10%); , the positive rate ≥ 10%), the serum CEA of the patient is required to exceed 10ug/L.
Those who have central nervous system metastasis or meningeal metastasis at the time of screening are judged by the investigator to be unsuitable for inclusion;
Participated in other clinical studies within 1 month before screening;
vaccinated with live attenuated vaccine within 4 weeks before screening;
Received the following anti-tumor treatments before screening: Received chemotherapy, targeted therapy or other experimental drug treatments within 14 days or at least 5 half-lives (whichever is shorter);
Parallel
CEA-targeted CAR-T cells
Biological/VaccineAdministration method: intravenous infusion； Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.
CEA-targeted CAR-T cells
Biological/VaccineAdministration method: intraperitoneal injection；Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.
To evaluate the safety of CAR-T cell preparations in the treatment of CEA-positive advanced malignancies [Safety and Tolerability]
The incidence of adverse events after CEA CAR-T cell infusion was assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0)
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
Assessing disease control rates of CAR-T cell preparations in CEA-positive advanced malignancies[Effectiveness]
Disease control rate: The proportion of subjects who achieved CR, PR, SD after CAR-T infusion accounted for all treated subjects (Assessed based on RECIST criteria)，the minimum value is 0%，maximum value is 100%, and higher scores mean a better outcome.
AUCS of CEA CAR-T cells [Cell dynamics]
AUCS is defined as the area under the curve in 90 days
CMAX of CEA CAR-T cells [Cell dynamics]
CMAX is defined as the highest concentration of CEA CAR-T cells expanded in peripheral blood
TMAX of CEA CAR-T cells[Cell dynamics]
TMAX is defined as the time to reach the highest concentration
Objective response rate (ORR) of CEA CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]
Objective response rate includes：The proportion of subjects who achieved CR, PR after CAR-T infusion accounted for all treated subjects (Assessed based on RECIST criteria)，the minimum value is 0%，maximum value is 100%, and higher scores mean a better outcome.
Duration of Response (DOR) of CEA CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]
DOR will be assessed from the first assessment of CR/PR/SD to the first assessment of recurrence or progression of the disease or death from any cause
Progress-free survival(PFS) of CEA CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]
PFS will be assessed from the first CEA-CAR-T cell infusion to death from any cause or the first assessment of progression(Assessed based on RECIST criteria)
Overall survival(OS)of CEA CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]
OS will be assessed from the first CEA-CAR-T cell infusion to death from any cause (Assessed by investigators based on IRECIST criteria)
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Chongqing Precision Biotech Co., Ltd
Lead sponsor
Shanxi Bethune Hospital
Collaborator
