Lung cancer is the leading cause of morbidity and mortality in the world, of which 80%-85% are non-small cell lung cancer (NSCLC). Most patients with NSCLC are at the advanced stage of diagnosis and have a poor prognosis. The 5-year survival rate of stage III patients is about 15%, the 5-year survival rate of stage IV patients is less than 5%, and the median survival time is only 7 months. CEACAM5 (CEA), also known as CD66e, is a classic tumor marker that has been used as a marker for many types of tumors for 50 years. It is mainly expressed in lung cancer, esophageal cancer, bile duct cancer, colorectal cancer, gastric cancer and other tumor types. In previous CAR-T-related clinical trials targeting CEA, the research team found that CAR-T cell preparations had a certain killing effect on CEA positive tumor cells. At the same time, CAR-T cell preparations cannot be sustained for a long time in the body, which is also a key factor restricting the anti-tumor effect of CAR-T cells in the body. To solve this problem, the killing ability and survival ability of CAR-T cell preparations on tumor cells in vitro and in vivo were improved by optimizing CAR structure and improving culture mode.
This study is a single-arm, open, enhanced 3+3 dose-ascending + dose-extending clinical study, aiming to evaluate the safety and efficacy of CAR T cell preparations, initially observe and study the pharmacokinetic characteristics of drugs in CEA positive advanced lung cancer patients, and obtain the recommended dose of CAR T cell preparations for CEA positive advanced lung cancer patients.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Subjects meeting the transfusion criteria will receive pre-treatment, which is as follows: fludarabine 25mg/m2/d×3day and cyclophosphamide 300mg/m2/d×3day, and intravenous CEA CAR-T therapy after 1-2 days of rest
Subjects meeting the reinfusion criteria will receive pre-treatment with fludarabine 25mg/m2/d×3day and cyclophosphamide 300mg/m2/d×3day, rest for 1-2 days, and intraperitoneal reinfusion targeted CEA CAR-T therapy
Wuhan Pulmonary Hospital
Wuhan, Hubei, China
RECRUITINGTo evaluate the safety and tolerability of CAR T cell preparations in the treatment of CEA positive advanced lung cancer【safety】
Adverse events and their proportion during the trial (assessed against the Common Terminology Standard for Adverse Events Version 5.0 (CTCAE 5.0) and ASTCT standards)
Time frame: 28days
To evaluate the disease control rate of CAR-T cell preparations in CEA positive advanced lung cancer【efficacy】
Disease control rates at 3 months were assessed according to Response Evaluation Criteria in Solid Tumors,Version 1.1 (RECIST 1.1), including CR, PR, and SD
Time frame: 3months
To evaluate the remission rate of CAR-T cell preparations in CEA positive advanced lung cancer【efficacy
Objective response rates at 3 months were assessed according to RECIST 1.1, including CR, PR
Time frame: 3months
To evaluate the overall survival of CAR-T cell preparations in CEA-positive advanced lung cancer【efficacy】
Overall survival (OS) : The time from the time the subject received CAR T cell retransfusion until death (from any cause)
Time frame: 2years
To evaluate the duration of response of CAR-T cell preparations in CEA-positive advanced lung cancer【efficacy】
Duration of response (DOR) : the time from the first evaluation of CR, PR, or SD to the first evaluation of disease recurrence or progression or death from any cause
Time frame: 2years
To evaluate the disease progression-free survival of CAR-T cell preparations in CEA-positive advanced lung cancer【efficacy】
Disease progression-free survival (PFS) : the time from the time the subject received CAR T cell therapy until the first disease progression or death from any cause
Time frame: 2years
To obtain the cytodynamics data of CAR-T cells in vivo【pharmacokinetics】
Cmax:The highest concentration of CAR T cells amplified in peripheral blood after reinfusion
Time frame: 3months
To obtain the cytodynamics data of CAR-T cells in vivo【pharmacokinetics】
Tmax:The time to reach the highest concentration of CAR-T cells in peripheral blood after reinfusion
Time frame: 3months
To obtain the cytodynamics data of CAR-T cells in vivo【pharmacodynamics】
The content of free CEA in peripheral blood at each time point after transfusion was determined by immunohistochemical method
Time frame: 2years
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