fhB7H3.CAR-Ts: fhB7H3.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: 30 mg/m2 i.v. for 3 consecutive days (Day -5\~Day -3)
Cyclophosphamide: 750 mg/m2 i.v. for once (Day -5)
Study summary
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
70 Years
Healthy volunteers
No
Inclusion Criteria:
1. Subjects should be 18-70 years old.
2. Subject has adequate performance status as defined by ECOG score of≤ 2.
3. Expected life expectancy is no less than 12 weeks.
4. Subjects must have histologically or cytologically confirmed unresectable, recurrent and / or metastatic hepatocellular carcinoma (HCC). And tumor tissues are measured positive for B7H3 expression.
5. Child-Pugh A, B grade.
6. Blood routine:
white blood cell count≥ 2.5 × 10\^9 / L; hemoglobin≥ 9 g/dL; platelet count≥ 50 × 10\^9 / L; lymphocyte proportion≥ 15 %;
7. Adequate organ function. Patients' main organs ( heart, lung, liver, kidney, etc. ) function well:
ALT and AST≤ 5 × ULN; ALB≥ 30 g/L； Total bilirubin≤ 2.5 × ULN； Serum creatinine\< 220μmol/L; Indoor oxygen saturation ≥ 95 %; Left ventricular ejection fraction≥ 40%;
8. No allergic reaction to contrast agents.
9. Procurement and T-cell production eligibility: a previously evaluation confirmed autologous peripheral blood mononuclear cells can be used for T-cell production.
10. Patients or their legal guardians voluntarily participate in and sign the informed consent form.
Exclusion Criteria:
1. The subject is a pregnant or lactating woman.
2. The subjects have infectious diseases (such as HIV, syphilis, active tuberculosis, etc.);
3. The subject has active infection or coagulation dysfunction.
4. Subjects with previous hepatic encephalopathy.
5. The subject is on anticoagulation or antiplatelet therapy.
6. The subject is an organ transplant or waiting for transplant.
7. Subjects with mental or psychological diseases who cannot cooperate with treatment and efficacy evaluation.
8. The subjects are highly allergic or have a history of severe allergies.
9. The subject has received chemotherapy/radiotherapy within the past 4 weeks.
10. The subject has a history of cellular immunotherapy or antibody therapy.
11. The subject is receiving systemic hormone therapy.
12. Subjects with systemic infection or severe local infection requiring anti-infection treatment.
13. The subject has dysfunction of important organs such as heart, lung, brain, liver, and kidney.
14. The subject is participating in other clinical research.
15. The doctor believes that there are other reasons not to be included in the treatment.
16. Unwilling or unable to provide consent/assent for participation in the study.
Primary outcome measure(s)
Safety of fhB7H3.CAR-T cells — 1 month 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 — 1 month 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.
Trial sites (1)
Facility
City
Region
Status
The Affiliated Hospital of Xuzhou Medical University
Xuzhou
Jiangsu
Recruiting
More The Affiliated Hospital of Xuzhou Medical University trials in China
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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