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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: mRNA HBV/TCR T-cells

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Royce Fam; Phone Number: 69260818; Email: royce.fam@liontcr.com

Study Locations

• Singapore
  • Singapore, Singapore, 169608
    • Recruiting
    • Singapore General Hospital
    • Contact: Thinesh L Krishnamoorthy; Phone Number: 62223322; Email: thinesh.l.krishnamoorthy@singhealth.com.sg
    • Contact: Email: thinesh.l.krishnamoorthy@singhealth.com.sg
    • Principal Investigator: Thinesh L Krishnamoorthy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status ≤1
2. 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
3. Serum HBsAg positivity
4. Non-cirrhotic or compensated cirrhosis Child-Pugh A (5 - 6 points)
5. Life expectancy of at least 3 months
6. 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:

1. Brain metastasis
2. 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
3. Use of immune checkpoint inhibitors and/or tyrosine kinase inhibitor (TKI) within 5 half-lives of the drug prior to baseline liver biopsy procedure
4. 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.
5. Likelihood to require any immunosuppressive treatments during the period of the clinical trial.
6. 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
7. Decompensated cirrhosis Child-Pugh B or C (7 - 15 points)
8. Concurrent administration of any other anti-tumour therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
9. Use of any investigational product (IP) or investigational medical device within 30 days of study drug administration
10. Serum HBV DNA levels ≥ 200 IU/ml at screening
11. Serum HBsAg levels ≥ 10,000 IU/ml at screening
12. Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples
13. Any condition or active infections which, in the investigator's opinion, makes the subject unsuitable for trial participation
14. Women who are pregnant or breast-feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mRNA HBV/TCR T-cells; Escalating regime from 1x10e5 to 5-10x10e6 cells/kg bodyweight (BW) every 2 weeks.	Drug: mRNA HBV/TCR T-cells; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Lion TCR Pte. Ltd.

Publications and helpful links

General Publications

• Koh S, Shimasaki N, Suwanarusk R, Ho ZZ, Chia A, Banu N, Howland SW, Ong AS, Gehring AJ, Stauss H, Renia L, Sallberg M, Campana D, Bertoletti A. A practical approach to immunotherapy of hepatocellular carcinoma using T cells redirected against hepatitis B virus. Mol Ther Nucleic Acids. 2013 Aug 13;2(8):e114. doi: 10.1038/mtna.2013.43.
• Kah J, Koh S, Volz T, Ceccarello E, Allweiss L, Lutgehetmann M, Bertoletti A, Dandri M. Lymphocytes transiently expressing virus-specific T cell receptors reduce hepatitis B virus infection. J Clin Invest. 2017 Aug 1;127(8):3177-3188. doi: 10.1172/JCI93024. Epub 2017 Jul 24.
• Tan AT, Yang N, Lee Krishnamoorthy T, Oei V, Chua A, Zhao X, Tan HS, Chia A, Le Bert N, Low D, Tan HK, Kumar R, Irani FG, Ho ZZ, Zhang Q, Guccione E, Wai LE, Koh S, Hwang W, Chow WC, Bertoletti A. Use of Expression Profiles of HBV-DNA Integrated Into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy. Gastroenterology. 2019 May;156(6):1862-1876.e9. doi: 10.1053/j.gastro.2019.01.251. Epub 2019 Jan 31.

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: January 25, 2021
• First Submitted That Met QC Criteria: February 8, 2021
• First Posted (Actual): February 9, 2021

Study Record Updates

• Last Update Posted (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Hepatitis B virus
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: LTCR-HCC-3-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No