This is single center, open-label phase I/II, non-randomized study which will enroll patients with recurrent advanced hepatocellular carcinoma to evaluate the safety, feasibility, and efficacy of fully human B7H3 CAR-T in treating hepatocellular carcinoma.
Subjects should be 18-70 years old.
Subject has adequate performance status as defined by ECOG score of≤ 2.
Expected life expectancy is no less than 12 weeks.
Subjects must have histologically or cytologically confirmed unresectable, recurrent and / or metastatic hepatocellular carcinoma (HCC). And tumor tissues are measured positive for B7H3 expression.
The subject is a pregnant or lactating woman.
The subjects have infectious diseases (such as HIV, syphilis, active tuberculosis, etc.);
The subject has active infection or coagulation dysfunction.
Subjects with previous hepatic encephalopathy.
Sequential
fhB7H3.CAR-Ts
Biological/VaccinefhB7H3.CAR-Ts will be transhepatic arterial infused after lymphodepletion. Three dose levels will be evaluated: Dose Level 1 (1×10\^6/kg), dose Level 2 (3×10\^6/kg) and dose Level 3 (5×10\^6/kg). If dose limiting toxicities (DLTs) are observed in each doses, Dose Level -1 (0.5×10\^6/kg /infusion) will be evaluated.
Fludarabine
Drug30 mg/m2 i.v. for 3 consecutive days (Day -5\~Day -3)
Cyclophosphamide
Drug750 mg/m2 i.v. for once (Day -5)
Safety of fhB7H3.CAR-T cells
Adverse events, including the type, frequency, severity and duration, such as cytokine release syndrome (CRS), on-target off-tumor, immune effector cell-associated neurotoxicity syndrome, will be monitored and assessed.
Objective response of fhB7H3.CAR-T cells
Objective response rate (ORR) including complete response (CR), partial response (PR), and/or stable disease, will be determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Complete Response (CR): disappearance of all target lesions, all target nodules must be reduced to normal size (short axis \<10 mm). Partial Response (PR): \>=30% decrease in the sum of the longest diameter of target lesions. Stable Disease (SD): no response or less response than Partial or Progressive. Progressive Disease (PD): 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
In vivo persistence of fhB7H3.CAR-T cells
Presence of CAR T cells in the peripheral blood will be assessed.
Progress free survival (PFS)
PFS will be assessed from the time of lymphodepletion prior to infusion of fhB7H3.CAR-Ts to progression (as defined per RECIST v1.1) or death.
Overall survival (OS)
Description: OS will be assessed from the date of lymphodepletion prior to infusion of fhB7H3.CAR-Ts to the date of death.
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The Affiliated Hospital of Xuzhou Medical University
Lead sponsor
Xuzhou Medical University
Collaborator
IIT MediTech Co. Ltd
Collaborator
