This is a phase I clinical study to evaluate the safety and tolerability of FAST targeted chimeric antigen receptor (CAR)-T cells (PTC13) in patients with carcinoembryonic antigen (CEA)-positive advanced malignant solid tumors, and to obtain the maximum tolerated dose of FAST CAR-T (PTC13) and phase II Recommended dose.
This is a single-center, open-label, dose-escalation and expansion study. The study includes one intraperitoneal infusion group only, with four dose levels: 2.0×10⁵ CAR+ cells/kg, 3.0×10⁵ CAR+ cells/kg, 4.0×10⁵ CAR+ cells/kg, and 5.0×10⁵ CAR+ cells/kg. Each dose level will initially enroll 3 to 6 patients using a standard 3+3 design to preliminarily evaluate safety and efficacy. Based on the comprehensive assessment by investigators and the technical collaborators, 1 to 2 recommended dose levels will be selected for dose expansion. In the expansion phase, an additional 6 to 12 patients will be enrolled to further evaluate safety and efficacy. The total planned enrollment is approximately 18 to 36 patients. Priority will be given to patients with peritoneal metastases from colorectal cancer.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Intraperitoneal infusion of FAST CEA-targeted CAR-T (PTC13); Subjects will be treated with Fludarabine and Cyclophosphamide based lymphodepleting chemotherapy before CAR-T cell infusion.
the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZU)
Hangzhou, Zhejiang, China
RECRUITINGIncidence of Adverse events after CEA-CAR-T cells infusion
Incidence and proportion of adverse events during the trial (evaluated per Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE 5.0) and ASTCT criteria)
Time frame: 28 days
Obtain the maximum tolerated dose of CEA-CAR-T cells
Dose-limiting toxicity after cell infusion
Time frame: 28 days
Disease control rate of CAR-T cell preparations in CEA-positive advanced malignancies
including complete response (CR), partial response (PR) and stable disease (SD)
Time frame: 3 months
Changes in serum tumor markers of CAR-T cell preparations in CEA-positive advanced malignancies
Tumor markers including CEA、 CA199、 CA125
Time frame: 3 months
Pharmacokinetic of CAR-T cells (Cmax)
The highest concentration of CAR-T cells in peripheral blood post-administration.
Time frame: 1 year
Pharmacokinetic of CAR-T cells (Tmax)
The time to reach the highest concentration
Time frame: 1 year
Pharmacokinetic of CAR-T cells (AUC28d/90d)
Area under the curve at 28 days/90 days
Time frame: 1 year
Pharmacodynamic of CAR-T cells
Levels of free CEA in peripheral blood at various time points.
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Time frame: 1 year