A Study of TCR-Redirected T Cell Infusion to Prevent Hepatocellular Carcinoma Recurrence 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 39 subjects with Hepatitis B virus (HBV) related HCC after liver transplantation. 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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A open-label, cohort clinical study of T cell receptor-redirected T cells to prevent recurrence of HBV-related hepatocellular carcinoma after liver transplantation. Subjects will be enrolled into the observation cohort or treatment cohort. Subjects enrolled in the treatment group will receive escalating doses of HBV/ TCR expressing autologous T cells after confirming eligibility. The interval between the first two doses is 14 days, followed by one month of safety monitoring, before subsequent two doses of 1 month interval in between. Thereafter, subjects would enter into observation period of the safety and tolerability of the treatment and will be followed up until disease relapse. Upon disease recurrence, eligible patient may receive HBV specific T-cell receptor (TCR-T) treatment.

Official Title
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A Phase I Study of T Cell Receptor-Redirected T Cell Infusion For Prevention of Hepatocellular Carcinoma Recurrence in Subjects With Hepatitis B Virus-Related Hepatocellular Carcinoma Post Liver Transplantation

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Biological: TCR-T
* Biological: No intervention and TCR-T (at crossover)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis as hepatocellular carcinoma (HCC) Underwent liver transplantation Seropositive for hepatitis B surface antigen (HBsAg), or presence of HBV DNA or HBV RNA before liver transplantation Expression of TCR-T target epitopes within specific human leukocyte antigen (HLA) class I profile No major post-operative complication Life expectancy of at least 3 months Ability to provide informed consent Ability to comply with study procedures Exclusion Criteria: Known, clinically suspected or has history or central nervous system (CNS) and bone metastasis Significant ongoing immunologic rejection based on pathology and clinical diagnosis Evidence or history of significant bleeding diathesis or coagulopathy Prior exposure to any cell therapy such as, but not limited to NK, CIK, DC, CTL, stem cells therapy Known history of testing positive for human immunodeficiency virus (HIV) 1 or 2 or known acquired immunodeficiency syndrome (AIDS) Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection Women who are pregnant or breast-feeding Any condition that is unstable or which could jeopardise the safety of the patient and his/her compliance in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Prevention
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HBV/TCR-T cell infusion<br>Subjects enrolled in the experimental (treatment) group will receive escalating doses of HBV/ TCR expressing autologous T cells. The interval between the first two doses is 14 days, followed by one month of safety monitoring, before subsequent two doses of 1 month interval in between. Thereafter, subjects would enter into observation period of the safety and tolerability of the treatment and will be followed up until disease relapse. | Biological: TCR-T<br>* Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR<br>|
| Other: No intervention and TCR-T (at crossover)<br>No intervention and to be crossover to experimental arm upon confirmation of disease recurrence. | Biological: No intervention and TCR-T (at crossover)<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 |
| --- | --- | --- |
| To Evaluate safety of the TCR-T treatment | Measures include - assessments of Adverse Events (AEs) and Serious AEs, | Start of Treatment until 28 days post last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate Progression Free Survival rate | PFS | Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first) | 
| To evaluate Duration of response rate | DOR | Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first) | 
| To evaluate objective response rate | ORR | Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCC, hepatocellular carcinoma, hepatitis B virus-related, post liver transplantation