A Study of TCR-Redirected T Cell Infusion in Subject With Recurrent HBV-related HCC Post Liver Transplantation

A Phase I Study T Cell Receptor-Redirected T Cells Infusions in Subjects With Recurrent HBV-Related Hepatocellular Carcinoma in Post Liver Transplantation

Hepatocellular carcinoma (HCC) recurrence rate is high among liver transplant patients, while treatment measures are limited. This study plans to recruit 10 patients with Hepatitis B virus (HBV) related HCC who underwent liver transplantation and are confirmed to have recurrent HCC. The objective of the study is to assess the safety, tolerability and effectiveness of the HBV specific T cell receptor (HBV/TCR) redirected T cell in the target population.

This is a phase I, single armed and open labelled trial in patients with recurrent HBV related HCC after liver transplantation. Subjects who meet eligibility criteria will receive escalating doses of HBV specific T cell receptor (TCR-T) on Day 1, Day 8, Day 15 and Day 22 of the first 28-day treatment cycle, followed by every 2-week dosing on Day 1, Day 15, Day 29 and Day 43 of repeated cycle. A 21-day treatment break will be given between each cycle. Treatment will be continued until disease progression unless otherwise specified per investigator's discretion. Subjects will be followed up post treatment for safety monitoring, including monthly follow up for the first three month and every 2-monthly follow up up to 24 months post treatment.

Inclusion Criteria:

• Diagnosis as hepatocellular carcinoma (HCC)
• Underwent liver transplantation and confirmed recurrent HCC post operation
• Seropositive for hepatitis B surface antigen
• No major post-operative complication
• Life expectancy of at least 12 weeks
• Ability to provide informed consent
• Ability to comply with study procedures
• HLA profile matching with HLA-class I restriction element of the available T cell receptors

Exclusion Criteria:

• Administration of any other cell therapy, including NK, CIK, DC, CTL, CAR-T, stem cells or combined therapy of the kind within 3 months prior to enrolment
• Second primary malignancy that is clinically detectable at the time of consideration for study enrolment
• Likelihood to require steroid treatment during the period of the clinical trial
• Any other concurrent liver infections such as hepatitis A, C or D infection
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
• Known Central Nervous System tumours including metastatic brain disease.
• Any condition that is unstable or which could jeopardise the safety of the patient and his/her compliance in the study
• Patients with reproductive potential who tested positive for serum or urine pregnancy test result within 14 days prior to enrolment.