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

• ClinicalTrials.gov Identifier: NCT04745403
• Recruitment Status: Recruiting
• First Posted: February 9, 2021
• Last Update Posted: July 1, 2022
• Sponsor: Lion TCR Pte. Ltd.
• Information provided by (Responsible Party): Lion TCR Pte. Ltd.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hepatocellular Carcinoma	Drug: mRNA HBV/TCR T-cells	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Tolerability Study of Redirected HBV-Specific T Cells in Patients With Hepatitis B Virus (HBV)-Related Hepatocellular Carcinoma (SAFE-T-HBV)
• Actual Study Start Date: May 20, 2022
• Estimated Primary Completion Date: July 1, 2023
• Estimated Study Completion Date: July 1, 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment [ Time Frame: Up to 4 years ]
   Objective response rate (ORR)
2. Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment [ Time Frame: Up to 4 years ]
   Progression free survival (PFS)
3. Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment [ Time Frame: Up to 4 years ]
   Overall survival (OS)

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Royce Fam; 69260818; royce.fam@liontcr.com

Locations

Singapore

Singapore General Hospital; Recruiting

Singapore, Singapore, 169608

Contact: Thinesh L Krishnamoorthy 62223322 thinesh.l.krishnamoorthy@singhealth.com.sg

Contact thinesh.l.krishnamoorthy@singhealth.com.sg

Principal Investigator: Thinesh L Krishnamoorthy

Sponsors and Collaborators

Lion TCR Pte. Ltd.

More Information

Publications of Results:

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.

• Responsible Party: Lion TCR Pte. Ltd.
• ClinicalTrials.gov Identifier: NCT04745403
• Other Study ID Numbers: LTCR-HCC-3-3
• First Posted: February 9, 2021
• Last Update Posted: July 1, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Lion TCR Pte. Ltd.:

Hepatitis B virus; Hepatocellular Carcinoma

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Hepatocellular; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases