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, it is divided into two subgroups: intravenous infusion and local infusion through the peritoneal cavity. Each subgroup includes a dose exploration stage (Part A) and a dose expansion stage (Part B). 3 patients were explored, starting from the low-dose group, and in the dose expansion phase, the safety and efficacy were further verified according to the safe recommended dose obtained in the dose exploration phase.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Administration method: intravenous infusion; Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.
Administration method: intraperitoneal injection;Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.
He'nan Cancer Hospital
Henan, China
RECRUITINGTo 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)
Time frame: 1 month
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
Time frame: 28 days
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.
Time frame: 3 month
AUCS of CEA CAR-T cells [Cell dynamics]
AUCS is defined as the area under the curve in 90 days
Time frame: 3 months
CMAX of CEA CAR-T cells [Cell dynamics]
CMAX is defined as the highest concentration of CEA CAR-T cells expanded in peripheral blood
Time frame: 3 months
TMAX of CEA CAR-T cells[Cell dynamics]
TMAX is defined as the time to reach the highest concentration
Time frame: 3 months
Pharmacodynamics of CEA CAR-T cells[Cell dynamics]
The content of CEA in peripheral blood was detected by ELISA at the visit points specified in the research protocol
Time frame: 3 months
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