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

NCT ID: NCT04745403

Last Updated: 2023-11-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-20
• Study Completion Date: 2028-07-01

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.

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

mRNA HBV/TCR T-cells

Escalating regime from 1x10e5 to 5-10x10e6 cells/kg bodyweight (BW) every 2 weeks.

Group Type: EXPERIMENTAL

mRNA HBV/TCR T-cells

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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).

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lion TCR Pte. Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Singapore General Hospital

Singapore, , Singapore

Site Status: RECRUITING

Countries

Singapore

Central Contacts

Royce Fam

Role: CONTACT

royce.fam@liontcr.com

69260818

Facility Contacts

Thinesh L Krishnamoorthy

Role: primary

thinesh.l.krishnamoorthy@singhealth.com.sg

62223322

Role: backup

thinesh.l.krishnamoorthy@singhealth.com.sg

References

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.

Reference Type: RESULT

PMID: 23941866 (View on PubMed)

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.

Reference Type: RESULT

PMID: 28737510 (View on PubMed)

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.

Reference Type: RESULT

PMID: 30711630 (View on PubMed)

Other Identifiers

LTCR-HCC-3-3

Identifier Type: -

Identifier Source: org_study_id