Back to resultsGPC3-CAR-T Cells for Immunotherapy of Cancer With GPC3 Expression
Primary Purpose
Hepatocellular Carcinoma, Immunotherapy, CAR
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
GPC3 and/or TGFβ targeting CAR-T cells
Sponsored by
About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Hepatocellular carcinoma, immunotherapy, CAR-T cell therapy, GPC3 or TGFβ targeting, Phase I clinical study, squamous cell lung cancer, interventional radiology, IL7-CCL19-secreting, SCFV against PD1/CTLA4/Tigit, knockdown of PD1/HPK1, DAP10
Eligibility Criteria
Inclusion Criteria:
- patients with advanced HCC,which express GPC3 protein.
- Life expectancy >12 weeks
- Child-Pugh-Turcotte score <7
- Adequate heart,lung,liver,kidney function
- 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
- 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;
- Tumor size more than 25cm;
- Severe virus infection such as HBV,HCV,HIV,et al
- Known HIV positivity
- History of liver transplantation
- 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
Other
Arm Label
CAR-T cell therapy group
Arm Description
Appropriate patients who could benefit from the GPC3 and TGFβ targeting CAR-T cell therapy against HCC are chosen to be the CAR-T cell therapy group.
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-T2-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
NCT03198546
First Posted
June 21, 2017
Last Updated
February 26, 2023
Sponsor
Second Affiliated Hospital of Guangzhou Medical University
Collaborators
Hunan Zhaotai Yongren Medical Innovation Co. Ltd., Guangdong Zhaotai InVivo Biomedicine Co. Ltd., First Affiliated Hospital, Sun Yat-Sen University
1. Study Identification
Unique Protocol Identification Number
NCT03198546
Brief Title
GPC3-CAR-T Cells for Immunotherapy of Cancer With GPC3 Expression
Official Title
CAR-T Cell Targeting GPC3 for Immunotherapy of Hepatocellular Carcinoma: 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, 2025 (Anticipated)
Study Completion Date
August 1, 2029 (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., First Affiliated Hospital, Sun Yat-Sen University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
Detailed Description
Choose appropriate patients with advanced hepatocellular carcinoma,with written consent for this study;
Perform biopsy to determine the expression of GPC3 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/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;
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;
Evaluate the clinical results as needed.
Will also perform the similar clinical trial on lung squamous carcinoma with the GPC3 expression.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma, Immunotherapy, CAR, GPC3 Gene Inactivation, T Cell, Squamous Cell Lung Cancer
Keywords
Hepatocellular carcinoma, immunotherapy, CAR-T cell therapy, GPC3 or TGFβ targeting, Phase I clinical study, squamous cell lung cancer, interventional radiology, IL7-CCL19-secreting, SCFV against PD1/CTLA4/Tigit, knockdown of PD1/HPK1, DAP10
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CAR-T cell therapy group
Arm Type
Other
Arm Description
Appropriate patients who could benefit from the GPC3 and TGFβ targeting CAR-T cell therapy against HCC are chosen to be the CAR-T cell therapy group.
Intervention Type
Biological
Intervention Name(s)
GPC3 and/or TGFβ targeting CAR-T cells
Intervention Description
Engineering GPC3 or/and TGFβ 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.
Primary Outcome Measure Information:
Title
Number of Patients with Dose Limiting Toxicity
Description
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.
Time Frame
three months
Secondary Outcome Measure Information:
Title
Percent of Patients with best response as either complete remission or partial remission.
Description
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.
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
Five years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
patients with advanced HCC,which express GPC3 protein.
Life expectancy >12 weeks
Child-Pugh-Turcotte score <7
Adequate heart,lung,liver,kidney function
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
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;
Tumor size more than 25cm;
Severe virus infection such as HBV,HCV,HIV,et al
Known HIV positivity
History of liver transplantation
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
Email
zhangzhf@gzhmu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Peng Li, PhD
Phone
+86 20 32015300
Email
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
Phone
+86-020-34153532
Email
zhangzhf@gzhmu.edu.cn
First Name & Middle Initial & Last Name & Degree
Deji Chen, MD,PhD
Phone
+86-020-34153532
Email
chendeji2003@163.com
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
28123387
Citation
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 Carcinoma. Front Immunol. 2017 Jan 11;7:690. doi: 10.3389/fimmu.2016.00690. eCollection 2016.
Results Reference
result
PubMed Identifier
34325726
Citation
Pang N, Shi J, Qin L, Chen A, Tang Y, Yang H, Huang Y, Wu Q, Li X, He B, Li T, Liang B, Zhang J, Cao B, Liu M, Feng Y, Ye X, Chen X, Wang L, Tian Y, Li H, Li J, Hu H, He J, Hu Y, Zhi C, Tang Z, Gong Y, Xu F, Xu L, Fan W, Zhao M, Chen D, Lian H, Yang L, Li P, Zhang Z. IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin. J Hematol Oncol. 2021 Jul 29;14(1):118. doi: 10.1186/s13045-021-01128-9.
Results Reference
derived
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GPC3-CAR-T Cells for Immunotherapy of Cancer With GPC3 Expression
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