Chimeric Antigen Receptor T Lymphocytes (CAR-T) Targeting CEA in the Treatment of CEA Positive Clinical Study of Advanced Malignant Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Gastric Cancer
- Sponsor
- Chongqing Precision Biotech Co., Ltd
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- To evaluate the safety of CAR-T cell preparations in the treatment of CEA-positive advanced malignancies [Safety and Tolerability]
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •At least one assessable lesion according to RECIST 1.1 criteria;
- •ECOG score 0-2 points;
- •No serious mental disorder;
- •Unless otherwise specified, the function of the vital organs of the subject shall meet the following conditions:
- •Blood routine: white blood cells\>3.0×10\^9/L, neutrophils\>0.8×10\^9/L, lymphocytes cells\>0.5×10\^9/L, platelets\>75×10\^9/L, hemoglobin\>80g/L;
- •Cardiac function: echocardiography showed cardiac ejection fraction ≥50%, and no obvious abnormality was found on electrocardiogram;
Exclusion Criteria
- •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);
- •Active infection or uncontrollable infection requiring systemic treatment;
- •Patients with intestinal obstruction, active gastrointestinal bleeding, or a history of gastrointestinal bleeding within 3 months;
- •Except for alopecia or peripheral neuropathy, the toxicity of previous anti-tumor therapy has not improved to the baseline level or ≤ grade 1;
- •Suffering from any of the following heart diseases:
- •New York Heart Association (NYHA) stage III or IV congestive heart failure;
- •Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months before enrollment;
Outcomes
Primary Outcomes
To evaluate the safety of CAR-T cell preparations in the treatment of CEA-positive advanced malignancies [Safety and Tolerability]
Time Frame: 1 month
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]
Time Frame: 28 days
Dose-limiting toxicity after CEA CAR-T cell infusion
Secondary Outcomes
- AUCS of CEA CAR-T cells [Cell dynamics](3 months)
- Assessing disease control rates of CAR-T cell preparations in CEA-positive advanced malignancies[Effectiveness](3 months)
- CMAX of CEA CAR-T cells [Cell dynamics](3 months)
- TMAX of CEA CAR-T cells[Cell dynamics](3 months)
- Pharmacodynamics of CEA CAR-T cells[Cell dynamics](3 months)