GPC3-CAR-T Cells for Immunotherapy of Cancer With GPC3 Expression
CAR-T Cell Targeting GPC3 for Immunotherapy of Hepatocellular Carcinoma: Phase I Clinical Trial
1 other identifier
interventional
30
1 country
2
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 hepatocellular-carcinoma
Started Jul 2017
Longer than P75 for phase_1 hepatocellular-carcinoma
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 21, 2017
CompletedFirst Posted
Study publicly available on registry
June 26, 2017
CompletedStudy Start
First participant enrolled
July 1, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 1, 2036
June 25, 2024
June 1, 2024
12.1 years
June 21, 2017
June 22, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (2)
Percent of Patients with best response as either complete remission or partial remission.
three months
Median CAR-T cell persistence
Five years
Study Arms (1)
CAR-T cell therapy group
OTHERAppropriate 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.
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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. -
You may not qualify if:
- 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. -
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
The First Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, 510072, China
The Second Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, 510260, China
Related Publications (2)
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.
PMID: 28123387RESULTPang 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.
PMID: 34325726DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Zhenfeng Zhang, MD,PhD
Second Affiliated Hospital of Guangzhou Medical University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 21, 2017
First Posted
June 26, 2017
Study Start
July 1, 2017
Primary Completion (Estimated)
August 1, 2029
Study Completion (Estimated)
August 1, 2036
Last Updated
June 25, 2024
Record last verified: 2024-06
Data Sharing
- IPD Sharing
- Will not share