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

Primary Purpose

Lung Cancer, Cancer, Immunotherapy

Status

Recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

CAR-T cells targeting GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring Lung Cancer, CAR-T Cell Therapy, PSCA, MUC1, HER2, Mesothelin, Lewis-Y, GPC3, AXL, EGFR, B7-H3, Claudin18.2, TGFβ, DAP10, HPK1, PD1, CTLA4, Tigit, Knockdown, SCFV

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

1. Patients with advanced cancer that expresses PSCA, MUC1, GPC3, AXL, EGFR or B7-H3 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 of PSCA, MUC1, GPC3, AXL, EGFR or B7-H3 CAR determined by flow-cytometry and killing of PSCA,MUC1,GPC3, AXL, EGFR, or B7-H3 -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. -

Sites / Locations

The First Affiliated Hospital of Sun Yat-sen UniversityRecruiting
The Second Affiliated Hospital of Guangzhou Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAR-T cell therapy group

Arm Description

Patients will receive 3 or more cycles of the CAR-T cells treatment via systemic or regional injection, from 1x10e6/kg-10x10e6/kg weight.

Outcomes

Primary Outcome Measures

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/TGFβ/HER2/Lewis-Y/AXL/EGFR-CAR T cells,which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5.

Secondary Outcome Measures

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.

Median CAR-T cell persistence

Median CAR-T cell persistence will be measured by quantitative rt-PCR.

Full Information

NCT ID

NCT03198052

First Posted

June 22, 2017

Last Updated

February 11, 2023

Sponsor

Second Affiliated Hospital of Guangzhou Medical University

Collaborators

Hunan Zhaotai Yongren Medical Innovation Co. Ltd., Guangdong Zhaotai InVivo Biomedicine Co. Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT03198052

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Recruiting

Study Start Date

July 1, 2017 (Actual)

Primary Completion Date

August 1, 2024 (Anticipated)

Study Completion Date

August 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Second Affiliated Hospital of Guangzhou Medical University

Collaborators

Hunan Zhaotai Yongren Medical Innovation Co. Ltd., Guangdong Zhaotai InVivo Biomedicine Co. Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lung Cancer, Cancer, Immunotherapy, CAR-T Cell

Keywords

Lung Cancer, CAR-T Cell Therapy, PSCA, MUC1, HER2, Mesothelin, Lewis-Y, GPC3, AXL, EGFR, B7-H3, Claudin18.2, TGFβ, DAP10, HPK1, PD1, CTLA4, Tigit, Knockdown, SCFV

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Model Description

Use engineered CAR-T cells to kill cancer cells with certain targets.

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

CAR-T cell therapy group

Arm Type

Experimental

Arm Description

Patients will receive 3 or more cycles of the CAR-T cells treatment via systemic or regional injection, from 1x10e6/kg-10x10e6/kg weight.

Intervention Type

Biological

Intervention Name(s)

CAR-T cells targeting GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR

Other Intervention Name(s)

Administration of CAR-T cells through vein or interventional technique.

Intervention Description

CAR-T cells injection: (1-10×10e6/kg CAR-T for each treatment; 3 or more cycles.

Primary Outcome Measure Information:

Title

Number of Patients with Dose Limiting Toxicity

Description

Time Frame

three months

Secondary Outcome Measure Information:

Title

Percent of Patients with best response as either complete remission or partial remission.

Description

Time Frame

three months

Title

Median CAR-T cell persistence

Description

Median CAR-T cell persistence will be measured by quantitative rt-PCR.

Time Frame

Six years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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. -

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Zhenfeng Zhang, MD,PhD

Phone

0086-020-34153532

zhangzhf@gzhmu.edu.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Peng Li, PhD

Phone

+86 20 32015300

lipeng@invivobio.com.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Zhenfeng Zhang, MD,PhD

Organizational Affiliation

Second Affiliated Hospital of Guangzhou Medical University

Official's Role

Principal Investigator

Facility Information:

Facility Name

The First Affiliated Hospital of Sun Yat-sen University

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510072

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Xianhong Xiang, MD,PHD

First Name & Middle Initial & Last Name & Degree

Yonghui Huang, MD,PHD

Facility Name

The Second Affiliated Hospital of Guangzhou Medical University

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510260

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Zhenfeng Zhang, MD,PhD

zhangzhf@gzhmu.edu.cn

First Name & Middle Initial & Last Name & Degree

Deji Chen, MD,PhD

Phone

+86-020-34153532

chendeji2003@163.com

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

28405515

Citation

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 Feb 6;6(3):e1284722. doi: 10.1080/2162402X.2017.1284722. eCollection 2017.

Results Reference

result

Learn more about this trial

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

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