Redirected HBV-Specific T Cells in Patients With HBV-related HCC (SAFE-T-HBV)

Study Overview
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Brief Summary
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This is a single center, single arm and open-label study to determine the safety of mRNA modified HBV-TCR redirected T-cells and to analyze the changes in tumor microenvironment caused by these HBV-TCR redirected T-cells in subjects with HBV-related HCC who are not amenable to/failed conventional treatment.

Official Title
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Safety and Tolerability Study of Redirected HBV-Specific T Cells in Patients With Hepatitis B Virus (HBV)-Related Hepatocellular Carcinoma (SAFE-T-HBV)

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: mRNA HBV/TCR T-cells


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status ≤1 Presence of primary hepatocellular carcinoma in the liver with presence of measurable tumour by RECIST 1.1 criteria, that is not amenable to, or failed, conventional treatment options Serum HBsAg positivity Non-cirrhotic or compensated cirrhosis Child-Pugh A (5 - 6 points) Life expectancy of at least 3 months HLA class 1 profile matching HLA-class I restriction element of the available T cell receptors (restricted by either HLA-A*02:01 or HLA-A*24:02). Key Exclusion Criteria: Brain metastasis Second primary malignancy that is clinically detectable at the time of consideration for study enrolment, except for in situ carcinoma of the cervix, non-melanoma skin carcinoma localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer and superficial bladder tumors Use of immune checkpoint inhibitors and/or tyrosine kinase inhibitor (TKI) within 5 half-lives of the drug prior to baseline liver biopsy procedure Alterations of concomitant medications which could potentially cause drug induced liver injury and affect liver biopsy result within 3 months of baseline liver biopsy procedure. Likelihood to require any immunosuppressive treatments during the period of the clinical trial. 7. Last RFA/TACE treatment within 3 months prior to first LioCyx-M infusion; Last Y90 therapy treatment within 6 months prior to first dose of mRNA HBV/TCR T-cells Decompensated cirrhosis Child-Pugh B or C (7 - 15 points) Concurrent administration of any other anti-tumour therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy. Use of any investigational product (IP) or investigational medical device within 30 days of study drug administration Serum HBV DNA levels ≥ 200 IU/ml at screening Serum HBsAg levels ≥ 10,000 IU/ml at screening Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples Any condition or active infections which, in the investigator's opinion, makes the subject unsuitable for trial participation Women who are pregnant or breast-feeding

Ages Eligible for Study
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Minimum Age: 21 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mRNA HBV/TCR T-cells<br>Escalating regime from 1x10e5 to 5-10x10e6 cells/kg bodyweight (BW) every 2 weeks. | Drug: mRNA HBV/TCR T-cells<br>* Study Infusion The first dose of mRNA HBV-TCR T-cells at dose 1x10e5/kg BW will be infused on Day 0, and subsequently incremental doses on Day 14 and 28, up to the dose of 5-10x10e6/kg BW.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety evaluation of mRNA HBV/TCR T-cell treatment | Based on incidence and severity of adverse events | Start of treatment until 28 days post last dose | 
| Analysis of modifications of tumour microenvironment caused by mRNA HBV/TCR T-cell treatment | Histological staining using biopsy and analysis of serum factors such as cytokines and chemokines | Start of treatment until end of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment | Objective response rate (ORR) | Up to 4 years | 
| Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment | Progression free survival (PFS) | Up to 4 years | 
| Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment | Overall survival (OS) | Up to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B virus, Hepatocellular Carcinoma