TCR-Redirected T Cells Therapy in Patient With HBV Related HCC

Study Overview
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Brief Summary
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This is a single center. single arm, open-label study to determine the safety and clinical benefit of TCR-redirected T cell therapy in patient with HBV related HCC post hepatectomy or radiofrequency ablation.

Official Title
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TCR-Redirected T Cells Therapy in Patient With HBV Related HCC

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Biological: TCR redirected T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Expression of the specific human leukocyte antigen (HLA) class I profile Hepatocellular carcinoma (HCC) with positive test for hepatitis B virus surface antigen (HBsAg) BCLC stage C At least 1 month after surgical intervention or 2 weeks after TACE (may include other type of resection/ablation) No major post-operative complication Laboratory criteria: Liver function: Child A, ALT < 200 U/L, AST < 200 U/L, Tbil < 17.1umol/L Renal Function: Creatinine clearance ≥ 60ml/minute Cardiac Function: No abnormality in cardiac enzyme and ECG Pulmonary Function (Lung): No abnormality in chest X-ray Sexually active subjects must be willing to use an acceptable method of contraception Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures Exclusion Criteria: Subject experiencing acute infection or gastric bleeding within 30 days Mid to late stage cirrhosis, i.e. Child-Pugh Score ≥ 7 Known history of testing positive for human immunodeficiency virus (HIV) Other liver complications, including alcoholic liver disease, non-alcoholic autoimmune liver disease, drug induced liver disease Serious systemic conditions, such as mental illness, cerebrovascular disease, coronary heart disease, diabetes, epilepsy Women who are pregnant or breast-feeding History of allergic reaction to blood products or investigational products History of chronic alcoholism or drug abuse/addiction Require systemic medications, such as steroids during the period of study drug administration Exposure to any cell therapy such as, but not limited to NK, CIK, DC, CTL, stem cells therapy 6 months prior to study drug administration Use of any investigational product (IP) or investigational medical device Any condition which could jeopardize 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: 70 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: TCR-Redirected T Cells<br>HBV antigen specific TCR redirected T cells | Biological: TCR redirected T cells<br>* HBV antigen specific TCR redirected T cell Infusions. Subjects will receive 1x10^4 - 5x10^6 TCR redirected T cells by IV infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety evaluation based in Incidences of adverse events/serious adverse events | Review the safety profile of T-Cell Therapy by assessing adverse/serious adverse events reported. | Up to 1 month after the last infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Tumour assessment will be according to mRECIST v1.1. This is based on percentage of participants with Complete Response (CR) and Partial Response (PR) according to mRECIST v1.1 from baseline. | Start of Treatment until first documented CR or PR, assessed up to 56 treatment weeks (protocol-defined treatment duration is until disease progression, death, or loss to follow up, whichever came first) | 
| Overall survival rate | Overall Survival (OS) defined as the time from randomisation until death by any cause. Participants will be followed up for survival follow up for at least five years. | Up to 5 years from the last infusion |