A Phase I Clinical Study of Chimeric Antigen Receptor T Cells Targeting Glypican-3 (CAR-GPC3 T Cells) in Patients with Advanced Hepatocellular Carcinoma
This is a phase I open-label, single-arm, multicenter clinical trial designed to observe and evaluate the safety, cell metabolokinetics, and efficacy of CAR-GPC3 T cells infused intravenously at single escalating doses in patients with advanced hepatocellular carcinoma. Primary objectives: \- To evaluate the safety and tolerability of CAR-GPC3 T cells infused intravenously at escalating doses in patients with advanced hepatocellular carcinoma. Secondary objectives: * To evaluate the metabolic kinetics of single infusion of CAR-GPC3 T cells * To evaluate the overall safety and tolerability of infusion of CAR-GPC3 T cells * To observe the efficacy of CAR-GPC3 T cells in the treatment of advanced hepatocellular carcinoma
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
CAR-GPC3 T Cells injection
Nanfang Hospital of Southern Medical University
Guangzhou, Guangdong, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, China
The 81st Hospital of Chinese PLA
Nanjing, Jiangsu, China
Renji Hospital Shang Hai Jiaotong Unversity of Medicine
Shanghai, Shanghai Municipality, China
Dose-limiting toxicity (DLT)
Safety
Time frame: After 28 days of single infusion
Maximum tolerated dose (MTD)
tolerability
Time frame: After 28 days of single infusion
Pharmacokinetics (the copies of cells in vivo)
Pharmacokinetics is the"Implantation endpoint" which is defined as the number of copies of CAR-GPC3 DNA in peripheral blood at each visit after infusion until any two consecutive test results are negative or below the detection limit. It aims to calculate the Peak Plasma Concentration (Cmax)
Time frame: Day0~Week 26
Pharmacokinetics ( the duration of survival of cells in vivo)
Duration of CAR-GPC3 T cell persistence is the period from the day of infusion to the first negative test result or result lower than the detection limit.It aims to calculate the area under the plasma concentration versus time curve (AUC)
Time frame: Day0~Week 26
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Adverse events up to 24 months of follow-up visit judged by the investigator to be associated with CAR-GPC3T cell infusion, such as abnormalities or changes in laboratory examinations, physical examinations, vital signs, etc.
Time frame: Month 24
Antitumor efficacy-Progression-free survival (PFS)
The period from the day when the subject receives the infusion of cells to the first recorded tumor progression (whether treated or not) or death of any cause, which occurs first.
Time frame: Month 24
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Zhongshan Hospital of Fudan University
Shanghai, Shanghai Municipality, China
The First Affiliated Hospital Zhejiang University
Hangzhou, Zhejiang, China
Antitumor efficacy-Duration of response (DOR)
The period from the first evaluation of CR or PR to the first evaluation of PD(Progressive Disease) or death of any cause.
Time frame: Month 24
Antitumor efficacy-Duration of disease control (DDC)
The period from the first evaluation of CR, PR, or SD to the first evaluation of PD or any cause of death.
Time frame: Month 24
Antitumor efficacy-Overall survival (OS)
The period from the first infusion to any cause of death
Time frame: Month 24
Antitumor efficacy-Objective response rate (ORR);
The number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%). In the event of PR or CR, the subjects should confirm it no less than 4 weeks after the first evaluation
Time frame: Month 24
Antitumor efficacy-Disease control rate (DCR)
The number of cases in which response (PR + CR) and stable disease (SD) are achieved from the start of cell infusion/the total number of evaluable cases (%).
Time frame: Month 24