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 single-arm, dose-escalation, open, exploratory clinical study to evaluate the safety and tolerability, preliminary efficacy and PK/PD characteristics of GPC3 CAR-T cells in the treatment of advanced hepatocellular carcinoma. Primary objectives: To evaluated the safety of GPC3 CAR-T cells in patients with advanced hepatocellular carcinoma. Secondary objectives:To evaluate the preliminary efficacy and PK/PD characteristics of CBG166.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
All subjects were intravenous administrated with CBG166.
First Affiliated Hospital, Medical College of Zhejiang University
Hangzhou, Zhejiang, China
RECRUITINGthe First Affiliated Hospital, School of Medicine, Zhejiang University
Hangzhou, Zhejiang, China
RECRUITINGDose limiting toxicity (DLT)
Describe the adverse events of limiting further increases in the dose of CBG166.
Time frame: Within 28 days of CAG166 infusion
Adverse events
Describe adverse events (AEs) and serious adverse events (SAEs) that are "likely" or "definitely" related to the study treatment that occur at any time of 24 months after treatment.
Time frame: Within 24 months after the treatment
Maximum tolerated dose
Determine the optimal agent for CBG166 CAR-T at maximum tolerated dose.
Time frame: From enrollment of the first subject to completion of follow-up of the last subject (up to 3 years)
Effectiveness evaluation
Objective response rate by RECIST 1.1
Time frame: At weeks 4, 8, and 18 and months 3, 4, 6, 9, 12, 15, 18 and 24 after cell infusion
Effectiveness evaluation
Progression-free survival by RECIST 1.1
Time frame: The efficacy is evaluated at weeks 4, 8, and 18 and months 3, 4, 6, 9, 12, 15, 18 and 24 after cell infusion
Effectiveness evaluation
Duration of response by RECIST 1.1
Time frame: The efficacy is evaluated at weeks 4, 8, and 18 and months 3, 4, 6, 9, 12, 15, 18 and 24 after cell infusion
Effectiveness evaluation
Time to response by RECIST 1.1
Time frame: The efficacy is evaluated at weeks 4, 8, and 18 and months 3, 4, 6, 9, 12, 15, 18 and 24 after cell infusion
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Effectiveness evaluation
Disease control time by RECIST 1.1
Time frame: The efficacy is evaluated at weeks 4, 8, and 18 and months 3, 4, 6, 9, 12, 15, 18 and 24 after cell infusion
Pharmacokinetic evaluation
Detect duration and expansion of CAR-T cells in vivo
Time frame: Within 24 months after the treatment
Pharmacodynamic evaluation
The copy number of HBV DNA in blood
Time frame: At weeks 4, 8, and 18 and months 3, 4, 6, 9, 12, 15, 18 and 24 after cell infusion
Pharmacodynamic evaluation
The serum level of IFN-α2
Time frame: At day 1, 4, 7, 15 and 21 and weeks 4, 8, and 18 and months 3, 4, 6, 9, 12, 15, 18 and 24 after cell infusion
Pharmacodynamic evaluation
The serum level of TGF-β
Time frame: At weeks 4, 8, and 18 and months 3, 4, 6, 9, 12, 15, 18 and 24 after cell infusion
Pharmacodynamic evaluation
The serum level of soluble AFP
Time frame: At weeks 4, 8, and 18 and months 3, 4, 6, 9, 12, 15, 18 and 24 after cell infusion
Pharmacodynamic evaluation
The serum level of soluble GPC3
Time frame: At weeks 4, 8, and 18 and months 3, 4, 6, 9, 12, 15, 18 and 24 after cell infusion
Pharmacodynamic evaluation
The serum levels of cytokine/chemokin
Time frame: At day 1, 4, 7, 15 and 21 and weeks 4, 8, and 18 and months 3, 4, 6, 9, 12, 15, 18 and 24 after cell infusion