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

Last updated: April 5, 2022
Sponsor: The Affiliated Hospital of Xuzhou Medical University
Overall Status: Active - Recruiting

Phase

1/2

Condition

Abdominal Cancer

Carcinoma

Liver Disorders

Treatment

N/A

Clinical Study ID

NCT05323201
XYFY2021-KL272-02
  • Ages 18-70
  • All Genders

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 Criteria

Inclusion

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, recurrentand / or metastatic hepatocellular carcinoma (HCC). And tumor tissues are measuredpositive 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 confirmedautologous peripheral blood mononuclear cells can be used for T-cell production.
  10. Patients or their legal guardians voluntarily participate in and sign the informedconsent form.

Exclusion

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 andefficacy 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-infectiontreatment.
  13. The subject has dysfunction of important organs such as heart, lung, brain, liver, andkidney.
  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.

Study Design

Total Participants: 15
Study Start date:
February 10, 2022
Estimated Completion Date:
February 10, 2027

Study 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.

Connect with a study center

  • The Affiliated Hospital of Xuzhou Medical University

    Xuzhou, Jiangsu 221002
    China

    Active - Recruiting

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