- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03198052
GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR-CAR-T Cells Against Cancers
CAR-T Targeting GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR for Immunotherapy of Lung Cancer: Phase I Clinical Trial
The third generation of CAR-T cells that target GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR have been constructed respectively and their anti-cancer function has been verified by multiple in vitro and in vivo studies.Clinical studies will be performed to test the anti-cancer function of the these individual or combination of the CAR-T cells for immunotherapy of human cancer patients with GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR expressions. In this phase I study, the safety, tolerance, and preliminary efficacy of the GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR
-CAR-T cell immunotherapy on human cancers will firstly be tested.
Study Overview
Status
Conditions
Detailed Description
- Choose appropriate patients with advanced lung or other cancers,with written consent for this study;
- Perform biopsy to determine the expression of HER2, Mesothelin, Lewis-Y, PSCA, MUC1, GPC3, AXL, EGFR, Claudin18.2, or B7-H3 of the tumor by western blotting or IHC;
- Collect blood from the patients and isolate mononuclear cells, activate the T cells and transfect the T cells with GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR targeting CAR, amplify the transfected T cells as needed, test the quality and killing activity of the CAR-T cells and then transfer them back the patients via systemic or local injections, and follow up closely to collect related results as needed;
To enhance the killing capability, CD4+ T cells are genetically engineered to express TGFβ-CAR and secret IL7/CCL19 and/or SCFVs against PD1/CTLA4/Tigit; CD8+T cells are constructed to express GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR
-DAP10-CAR with knockdown of PD1/HPK1;
- Other cancers with these cell surface antigen expressions are also recruited if needed;
- Evaluate the clinical results as needed.
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Guangdong
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Guangzhou, Guangdong, China, 510260
- Recruiting
- The Second Affiliated Hospital of Guangzhou Medical University
-
Guangzhou, Guangdong, China, 510072
- Recruiting
- The First Affiliated Hospital of Sun Yat-Sen University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
1. Patients with advanced cancer that expresses GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR protein; 2. Life expectancy >12 weeks; 3. Adequate heart,lung,liver,kidney function; 4. Available autologous transduced T cells with greater than or equal to 20% expression ofGPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR-CAR determined by flow-cytometry and killing of GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR-positive targets greater than or equal to 20% in cytotoxicity assay; 5. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
-
Exclusion Criteria:
- Had accepted gene therapy before;
- Severe virus infection such as HBV,HCV,HIV,et al;
- Known HIV positivity;
- Active infectious disease related to bacteria, virus,fungi,et al;
- Other severe diseases that the investigators consider not appropriate;
- Pregnant or lactating women;
- Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day);
- Other conditions that the investigators consider not appropriate. -
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: CAR-T cell therapy group
Patients will receive 3 or more cycles of the CAR-T cells treatment via systemic or regional injection, from 1x10e6/kg-10x10e6/kg weight.
|
CAR-T cells injection: (1-10×10e6/kg CAR-T for each treatment; 3 or more cycles.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Patients with Dose Limiting Toxicity
Time Frame: three months
|
A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR-CAR T cells,which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5.
|
three months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent of Patients with best response as either complete remission or partial remission.
Time Frame: three months
|
Response rates will be estimated as the percent of patients whose best response is either complete remission or partial remission by combining the data from the patients.
To compare with historical data, a 95% confidence interval will be calculated for the response rate.
|
three months
|
Median CAR-T cell persistence
Time Frame: Six years
|
Median CAR-T cell persistence will be measured by quantitative rt-PCR.
|
Six years
|
Collaborators and Investigators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- ZZCART-002
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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