The purpose of this study is to evaluate the safety and efficacy of allogeneic γδ T cells combined with targeted therapy and PD-1 monoclonal antibody in patients with hepatocellular carcinoma resistant to PD-1 monoclonal antibody. Hepatocellular Carcinoma
This is a double-arm, single-center, randomized, open label phase I clinical trial to evaluate the efficacy and safety of the combination of ex-vivo expanded allogeneic γδ T cells plus targeted therapy and PD-1 monoclonal antibody in patients with BCLC stage B or C hepatocellular carcinoma (HCC). A typical 3+3 dose-escalation design will be used to determine the optimal dose level of γδ T cells based on the incidence of dose-limiting toxicity (DLT). The initial infusion dose level will start from 1×10\^8/kg to 4×10\^8/kg in every 3 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Cells will be extracted from a healthy donor by apheresis, followed by ex-vivo expansion and activation. The ex-vivo expanded γδ T cells from donors will be adoptively transfused.
Humanized programmed death receptor (PD-1) monoclonal antibody that binds to PD- and prevents binding of PD-1 with programed death ligands 1 (PD-L1) and PD-L2. It can function to activate cytotoxic T lymphocytes and inhibit tumor growth.
Multi-target kinase inhibitors can act on VEGFR-1,VEGFR-2,VEGFR-3,FGFR1,PDGFR,cKit,Ret and other targets.
Safety evaluation: Incidence of Adverse events (AEs)
Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).
Time frame: up to 60 weeks
Safety evaluation: Dose limited toxicity (DLTs)
The incidence, characteristic and severity of DLTs will be recorded and assessed.
Time frame: up to 60 weeks
Efficacy evaluation: Objective Response Rate(ORR)
Objective clinical response will be assessed by investigators up to 15months
Time frame: up to 15months
Efficacy evaluation: Duration of Response(DOR)
he duration of objective response in patients will be recorded until 15months after the start of 1st cycle of treatment
Time frame: up to 15months
Efficacy evaluation: Progress Free Survival(PFS)
Observation for progression-free survival (PFS) will be recorded until 15 months after the start of 1st cycle of treatment
Time frame: up to 15months
Efficacy evaluation: Overall Survival (OS)
Observation for overall survival l (OS) will be recorded until 15 months after the start of 1st cycle of treatment.
Time frame: up to 15months
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