TCR-Redirected T Cell Treatment in Patients With Recurrent HBV-related Hepatocellular Carcinoma Post Liver Transplantation

Study Overview
=================
Brief Summary
-----------------
This is a single-arm and open-label study to assess the safety, tolerability and primary efficacy of the HBV specific T cell receptor (HBV/TCR) redirected T cell in patients with recurrent Hepatitis B virus (HBV) related hepatocellular carcinoma post liver transplantation.

Official Title
-----------------
Phase I Study of T Cell Receptor-Redirected T Cells With Recurrent HBV Treatment in Patients-Related Hepatocellular Carcinoma in Post Liver Transplantation

Conditions
-----------------
Recurrent Hepatocellular Carcinoma

Intervention / Treatment
-----------------
* Biological: TCR-T cells


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis as hepatocellular carcinoma (HCC). Recurrent locally advanced and/or metastatic hepatocellular carcinoma (HCC) post liver transplantation. Seropositive for hepatitis B surface antigen, or presence of HBV DNA or HBV RNA. HLA profile matching with HLA-class I restriction element of the available T cell receptors. ECOG performance status ≤ 2. Laboratory criteria: Liver function: ALT and AST ≤ 5 of upper limit of normal (ULN), TBIL ≤ 3 x ULN. Neutrophil cell number ≥1.5×10^9/L. Platelet count ≥100×10^9/L. Ability to provide informed consent. Willing and able to comply with all study procedures. Exclusion Criteria: 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. Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples. Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection. Administration of any other cell therapy, including NK, CIK, DC, CTL, CAR- T, stem cells or combined therapy of the kind within 28 days prior to start of treatment. 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
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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>Autologous T cells with HBV antigen-specific TCR | Biological: TCR-T cells<br>* Patients will receive 1 x 10^4 cells/kg to 5 x 10^6 cells/kg bodyweight of TCR redirected T cells by IV infusion.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety evaluation of the TCR-T treatment | Incidence of adverse events/serious adverse events | Start of Treatment until 28 days post last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Tumour assessment will be according to RECIST v1.1. This is based on percentage of participants with Complete Response (CR) and Partial Response (PR) according to RECIST v1.1 from baseline. | Start of treatment until disease progression, and subsequent follow up up to 24 months post treatment. | 
| Progression-free survival (PFS) | 1-year PFS is measured by the number of patients with stable disease after 1 year, using RECIST v1.1. | Start of treatment until disease progression, and at 6-month and 1-year. | 
| Overall survival (OS) | OS is defined as the time from randomisation until death by any cause. Participants will be followed up for survival follow up for two years. | Start of treatment until disease progression, and at 6-month and 1-year. |