A Phase I Clinical Study of 4th generation 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 and multiple infusion, dose escalation/cohort expansion study to evaluate the safety, cell pharmacokinetics, and preliminary efficacy of CAR-GPC3 T cells, infused intravenously in subjects who have been diagnosed with GPC3 positive advanced hepatocellular carcinoma and refractory or intolerant to current standard systemic treatment. 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 cellular pharmacokinetics of CAR-GPC3 T cells * To evaluate the overall safety and tolerability of infusion of CAR-GPC3 T cells * To investigate the preliminary efficacy of CAR-GPC3 T cells in the treatment of advanced hepatocellular carcinoma
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Pretreatment with fludarabine and cyclophosphamide CAR-GPC3 T Cells infusion
First affiliated hospital, Zhejiang University
Hangzhou, Zhejiang, China
Dose limited toxicity and Maximum Tolerated Dose
Safety and tolerability
Time frame: After 28 days of single infusion
Number of cells
1.the number of cell copies and cell persistence duration in peripheral blood) Pharmacokinetics is the "Implantation endpoint" which is defined as the number of copies of the CAR-GPC3 DNA in peripheral blood detected at each visit after infusion until any two consecutive test results are negative or below the detection limit. 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
Time frame: Through week 52 or the second timepoint of cells undetectable
Number of participants with treatment-related adverse events
Adverse events occurring through18 weeks and 52weeks post infusion, such as abnormalities or changes in laboratory examinations, physical examinations, vital signs, etc. Adverse events occurring through18 weeks and 52weeks post infusion, such as abnormalities or changes in laboratory examinations, physical examinations, vital signs, etc.
Time frame: Through study completion, an average of 3 years
Antitumor efficacy-Progression-free survival (PFS)
The period from the day when the subject receives the first study treatment to the first recorded tumor progression (whether treated or not) or death of any cause, which occurs first
Time frame: Through study completion, an average of 3 years
Antitumor efficacy-Duration of response (DOR)
The period from the first evaluation of CR or PR to the first evaluation of PD or death of any cause.
Time frame: Through study completion, an average of 3 years
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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: Through study completion, an average of 3 years
Antitumor efficacy-Overall survival (OS)
The period from the first study treatment to any cause of death
Time frame: Through study completion, an average of 3 years
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: Through study completion, an average of 3 years
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: Through study completion, an average of 3 years