This is a single-arm, open, dose-increasing phase I clinical study to explore the safety, tolerability and pharmacokinetic characteristics of the drug C-13-60 cells, and preliminarily observe the efficacy of the drug in CEA positive late malignant solid tumors, and explore the applicable dose regimen for phase II clinical trials.
Age ≥18 years old, male or female;
Patients with advanced malignant solid tumors confirmed by histology or pathology, including colorectal cancer, esophageal cancer, gastric cancer, pancreatic cancer, non-small cell lung cancer, breast cancer, and cholangiocarcinoma;
Advanced colorectal cancer: progression or intolerance or inadequacy after third-line standard therapy including cetuximab ± Irinotecan/regorafenib /fruquintinib/trifluridine；
Advanced or metastatic esophageal cancer/esophagogastric junction cancer: patients with esophageal cancer who progress or are intolerant or inapplicable after second-line therapy including PD-1 MAB /PD-L1 mab; Patients with esophagogastric junction cancer progressed or were intolerant or inapplicable after second-line therapy including taxane or irinotecan or PD-1 /PD-L1 monoclonal antibody; For HER-2 positive patients, trastuzumab containing system therapy should fail or be intolerable or not applicable;
People who have received CAR-T therapy or other gene-modified cell therapy;
Patients with BMS with clinical symptoms or lesions located in key parts of the brain at the time of screening, patients with BMS without clinical symptoms or lesions located in non-critical parts of the brain should be evaluated by researchers or specialists to gain more than the risk.
Received other investigational drugs or treatments that are not on the market within 4 weeks prior to screening;
Received live attenuated vaccine within 4 weeks prior to screening;
Sequential
CEA-targeted CAR-T cells
Biological/VaccineAdministration method: intravenous infusion； Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.
To determine the dose range and DLT of C-13-60 cells for CEA positive advanced malignant solid tumors [Safety and Tolerability]
The incidence of adverse events (TEAE) after treatment; Incidence of treatment-related adverse events; Adverse evens of Special Interest (AESI);
To obtain the maximum tolerable dose of C-13-60 cells [Safety and Tolerability]
Incidence and number of dose-limiting toxicity (DLT) cases，Dose-limiting toxicity after CAR-T cell infusion
Disease control rate (DCR) within 3 months after infusion of C-13-60 cell preparation[Effectiveness]
Disease control rate: The proportion of subjects who achieved complete response (CR), partial response (PR), stable disease (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.
Area under the curve (AUCS) of C-13-60 cell [Cell dynamics]
AUCS is defined as the area under the curve in 90 days
Maximum concentration (CMAX) of C-13-60 cell [Cell dynamics]
CMAX is defined as the highest concentration of CEA CAR-T cells expanded in peripheral blood
Maximum time (TMAX) of C-13-60 cell[Cell dynamics]
TMAX is defined as the time to reach the highest concentration
Objective response rate (ORR) of C-13-60 cell 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 C-13-60 cell 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 C-13-60 cell treatment in patients with CEA-positive advanced malignancies[Effectiveness]
PFS will be assessed from the first CAR-T cell infusion to death from any cause or the first assessment of progression(Assessed based on RECIST criteria)
Overall survival(OS) of C-13-60 cell treatment in patients with CEA-positive advanced malignancies[Effectiveness]
OS will be assessed from the first CAR-T cell infusion to death from any cause (Assessed by investigators based on RECIST criteria)
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Chongqing Precision Biotech Co., Ltd
Lead sponsor
Zhejiang University
Collaborator
