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

Hepatocellular Carcinoma Clinical Trial

— SAFE-T-HBV  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04745403
• Other study ID #: LTCR-HCC-3-3
• Status: Recruiting
• Phase: Phase 1
• Start date: May 20, 2022
• Est. completion date: July 1, 2028

Study information

• Verified date: November 2023
• Source: Lion TCR Pte. Ltd.
• Contact: Royce Fam
• Phone: 69260818
• Email: royce.fam[@]liontcr.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: July 1, 2028
• Est. primary completion date: July 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

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.

Locations

Country	Name	City	State
Singapore	Singapore General Hospital	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
Lion TCR Pte. Ltd.

Country where clinical trial is conducted

Singapore, 

References & Publications (3)

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/JCI9302 — View Citation

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 — View Citation

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 Geno — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment	Objective response rate (ORR)	Up to 4 years
Secondary	Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment	Progression free survival (PFS)	Up to 4 years
Secondary	Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment	Overall survival (OS)	Up to 4 years