Anti-CEA CAR-T for Advanced CEA-Positive Lung Carcinoma
ConditionAdvanced Lung Cancer
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorChongqing Precision Biotech Co., Ltd
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥18 years old, male or female;
histologically or pathologically confirmed advanced, metastatic or recurrent lung cancer, including non-small cell lung cancer and small cell lung cancer;
Progression or intolerance (including but not limited to surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc.) after receiving at least second-line standard therapy, patients with driver gene positive non-small cell lung cancer need to receive corresponding targeted therapy for disease progression or intolerance. Patients with driver negative non-small cell lung cancer or small cell lung cancer need to receive platinum-containing chemotherapy for disease progression or intolerance;
Immunohistochemical staining of tumor samples within 3 months confirmed CEA positive (clear membrane staining, positive rate ≥10%); If the immunohistochemical results of tumor samples are more than 3 months from the time of screening (clear membrane staining, positive rate ≥10%), the patient's serum CEA should exceed 10ug/L.
Disqualifiers
Patients with central nervous system metastasis or meningeal metastasis with clinical symptoms at the time of screening, or with other evidence that the central nervous system metastasis or meningeal metastasis was not controlled, and the investigators judged that they were not suitable for inclusion;
Participating in other clinical studies within 1 month before screening;
Received live attenuated vaccine within 4 weeks prior to screening;
have received any of the following anti-tumor therapies prior to screening: chemotherapy, targeted therapy, or other investigational agents within 14 days or at least 5 half-lives, whichever is shorter;
Trial design
Design model
Parallel
Treatments tested in this trial
Targeted CEA CAR-T
Biological/VaccineSubjects 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
Targeted CEA CAR-T
Biological/VaccineSubjects 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
Treatment groups
60 Participants
are divided into 2 treatment groupsGroup A: Targeted CEA CAR-T intravenous infusion groupExperimental treatment 1 intervention
Group B: Targeting CEA CAR-T pleural infusion groupExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
To 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
28daysSecondary outcomes
1
To evaluate the disease control rate and remission rate of CAR-T cell preparations in CEA positive advanced lung cancer【efficacy】
1）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； 2）Objective response rates at 3 months were assessed according to RECIST 1.1, including CR, PR；
Time frame
3months2
To evaluate the survival benefit of CAR-T cell preparations in CEA-positive advanced lung cancer【efficacy】
1）Overall survival (OS) : The time from the time the subject received CAR T cell retransfusion until death (from any cause)； 2）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; 3）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
2years3
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
3months4
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
3monthsSponsors and contacts
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Source ClinicalTrials.gov