GPC3-CAR-T Cells for Immunotherapy of Cancer With GPC3 Expression

Hepatocellular Carcinoma Clinical Trial

Official title:

CAR-T Cell Targeting GPC3 for Immunotherapy of Hepatocellular Carcinoma: Phase I Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03198546
• Other study ID #: ZZCART-003
• Status: Recruiting
• Phase: Phase 1
• Start date: July 1, 2017
• Est. completion date: August 1, 2029

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/fourth generation of CAR-T cells that target GPC3 (GPC3-CART cell) and/or soluble TGFβ (GPC3/TGFβ-CART )have been constructed and their anti-HCC function has been verified by multiple in vitro and in vivo studies. Clinical studies will be performed to test the anti-cancer function by the GPC3/TGFβ-CAR-T cells in human HCC patients with GPC3 expression. In this phase I study, the safety, tolerance, and preliminary efficacy of the GPC3/TGFβ-CAR-T cell immunotherapy on human will firstly be tested.

Description:

1. Choose appropriate patients with advanced hepatocellular carcinoma,with written consent for this study;

2. Perform biopsy to determine the expression of GPC3 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/TGFβ targeting CAR (or/and scfv/cytokines-secreting), amplify the number of transfected T cells as needed, test the quality and killing activity of the GPC3/TGFβ-CART cells and then transplant back the patients via systemic or local infusions (via artery or intra-tumor), 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-DAP10-CAR with knockdown of PD1/HPK1;

5. Evaluate the clinical results as needed.

6. Will also perform the similar clinical trial on lung squamous carcinoma with the GPC3 expression.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: August 1, 2029
• Est. primary completion date: August 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. patients with advanced HCC,which express GPC3 protein.

2. Life expectancy >12 weeks

3. Child-Pugh-Turcotte score <7

4. Adequate heart,lung,liver,kidney function

5. Available autologous transduced T cells with greater than or equal to 20% expression of GPC3 CAR determined by flow-cytometry and killing of GPC3-positive targets greater than or equal to 20% in cytotoxicity assay

6. 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. Tumor size more than 25cm;

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

4. Known HIV positivity

5. History of liver transplantation

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

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

8. Pregnant or lactating women

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

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

Related Conditions & MeSH terms

• CAR
• Carcinoma
• Carcinoma, Hepatocellular
• GPC3 Gene Inactivation
• Hepatocellular Carcinoma
• Immunotherapy
• Squamous Cell Lung Cancer
• T Cell

Intervention

Biological:
• GPC3 and/or TGFß targeting CAR-T cells
Engineering GPC3 or/and TGFß targeting CAR combined with/or without IL7/CCL19 and/or scfv against PD1/CTLA4/Tigit secreting vector into T cells with knockdown of PD1/HPK1, which are isolated from patients with advanced HCC, and then transfusing them back the patients.

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 (4)

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

Country where clinical trial is conducted

China, 

References & Publications (1)

Jiang Z, Jiang X, Chen S, Lai Y, Wei X, Li B, Lin S, Wang S, Wu Q, Liang Q, Liu Q, Peng M, Yu F, Weng J, Du X, Pei D, Liu P, Yao Y, Xue P, Li P. Anti-GPC3-CAR T Cells Suppress the Growth of Tumor Cells in Patient-Derived Xenografts of Hepatocellular Carci — 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-T2-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.	Five years