GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR-CAR-T Cells Against Cancers

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03198052
• Other study ID #: ZZCART-002
• Status: Recruiting
• Phase: Phase 1
• Start date: July 1, 2017
• Est. completion date: August 1, 2026

Study information

• Verified date: February 2023
• Source: Second Affiliated Hospital of Guangzhou Medical University
• Contact: Zhenfeng Zhang, MD,PhD
• Phone: 0086-020-34153532
• Email: zhangzhf[@]gzhmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

1. Choose appropriate patients with advanced lung or other cancers,with written consent for this study;

2. 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;

3. 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;

4. 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;

5. Other cancers with these cell surface antigen expressions are also recruited if needed;

6. Evaluate the clinical results as needed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: August 1, 2026
• Est. primary completion date: August 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Patients with advanced cancer that expresses GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFß/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, TGFß, HER2, Lewis-Y, AXL, or EGFR-CAR determined by flow-cytometry and killing of GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFß, 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:

1. Had accepted gene therapy before;

2. Severe virus infection such as HBV,HCV,HIV,et al;

3. Known HIV positivity;

4. Active infectious disease related to bacteria, virus,fungi,et al;

5. Other severe diseases that the investigators consider not appropriate;

6. Pregnant or lactating women;

7. Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day);

8. Other conditions that the investigators consider not appropriate. -

Related Conditions & MeSH terms

• Cancer
• CAR-T Cell
• Immunotherapy
• Lung Cancer
• Lung Neoplasms

Intervention

Biological:
• CAR-T cells targeting GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFß, HER2, Lewis-Y, AXL, or EGFR
CAR-T cells injection: (1-10×10e6/kg CAR-T for each treatment; 3 or more cycles.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong
China	The Second Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong

Sponsors (3)

Lead Sponsor	Collaborator
Second Affiliated Hospital of Guangzhou Medical University	Guangdong Zhaotai InVivo Biomedicine Co. Ltd., Hunan Zhaotai Yongren Medical Innovation Co. Ltd.

Country where clinical trial is conducted

China, 

References & Publications (1)

Wei X, Lai Y, Li J, Qin L, Xu Y, Zhao R, Li B, Lin S, Wang S, Wu Q, Liang Q, Peng M, Yu F, Li Y, Zhang X, Wu Y, Liu P, Pei D, Yao Y, Li P. PSCA and MUC1 in non-small-cell lung cancer as targets of chimeric antigen receptor T cells. Oncoimmunology. 2017 Fe — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients with Dose Limiting Toxicity	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/TGFß/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	Percent of Patients with best response as either complete remission or partial remission.	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
Secondary	Median CAR-T cell persistence	Median CAR-T cell persistence will be measured by quantitative rt-PCR.	Six years