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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Recurrent Hepatocellular Carcinoma

Intervention / Treatment
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* Biological: Biological: TCR-T


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HBV/TCR T cell Infusion<br>This is a single-arm study. Patients will receive a total of 2 cycles, in which first 28-day treatment cycle consists of escalating doses of TCR-T on Day 1, Day 8, Day 15 and Day 22, followed by every 2-week dosing on Day 1, Day 15, Day 29 and Day 43 of second (final) cycle. A one month treatment break will be given between the cycles. | Biological: Biological: TCR-T<br>* Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of the TCR-T treatment |  | Start of treament until 1 month after last treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of induction of tumor specific T cell responses as measured by the persistence of HBV specific T cells in peripheral blood samples at several time points following adoptive transfer |  | Start of treatment until disease progression, and subsequent follow up up to 24 months post treatment | 
| Systemic release of inflammatory cytokines after administration of transduced T cells compared to baseline |  | Start of treatment until disease progression, and subsequent follow up up to 24 months post treatment |