NCT05323201

Study Of B7H3 CAR-T Cells in Treating Advanced Liver Cancer

A Single-Arm, Open-Label Study to Evaluate Safety and Efficacy of B7H3 or HBsAg Targeting CAR-T in Treating Advanced Hepatocellular Carcinoma

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: The Affiliated Hospital of Xuzhou Medical University · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Chimeric antigen-modified T cells are genetically modified T cells that use gene transduction technology to introduce CARs, containing tumor antigen-specific recognition single-chain antibodies and T cell activation motifs, into patient T cells, so that these transduction CAR-T cells can directly recognize the specific antigen on tumor cells, thereby killing tumor cells. Previous studies have confirmed that B7H3 is highly expressed in hepatocellular carcinoma cell lines, which is negatively correlated with the ten-year survival of patients. It is suggested that B7H3 is a specific therapeutic target for liver cancer. The purpose of this study is to test the safety and efficacy of a newly developed fully human scFv-armed B7H3 targeting chimeric antigen receptor T cells (fhB7H3.CAR-Ts), which are supposed to attack and eliminate B7H3-positive cancer cells. The investigators designed a single-arm open-label clinical study, the participants' peripheral blood mononuclear cells will be collected and used to manufacture fhB7H3.CAR-Ts. Before infusion, the patients will receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine for three consecutive days. Two days later after lymphodepletion, the fhB7H3.CAR-Ts would be given through transhepatic arterial infusion. From the day of infusion, participants' peripheral blood will be collected twice a week in the first month to monitor the survival of fhB7H3.CAR-Ts and evaluate the therapeutic efficacy. Additional follow-up and examination will be performed monthly for the first three month and then trimonthly until two year. Thereafter, annual follow-up will be completed for 5 years. This is an investigator-initiated clinical study to assess clinical performance of novel fhB7H3.CAR-Ts which may help other advanced and recurrent liver cancer patients in the future.

Conditions

• Hepatocellular Carcinoma

Interventions

Type	Name	Description
BIOLOGICAL	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.
DRUG	Fludarabine	30 mg/m2 i.v. for 3 consecutive days (Day -5\~Day -3)
DRUG	Cyclophosphamide	750 mg/m2 i.v. for once (Day -5)

Timeline

• Start date: 2022-02-10
• Primary completion: 2024-02-10
• Completion: 2027-02-10
• First posted: 2022-04-12
• Last updated: 2022-04-12

Locations

1 site across 1 country: China