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

Primary Purpose

Hepatocellular Carcinoma

Status

Recruiting

Phase

Phase 1

Locations

Singapore

Study Type

Interventional

Intervention

mRNA HBV/TCR T-cells

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Hepatitis B virus, Hepatocellular Carcinoma

Eligibility Criteria

21 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Singapore General HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

mRNA HBV/TCR T-cells

Arm Description

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

Outcomes

Primary Outcome Measures

Safety evaluation of mRNA HBV/TCR T-cell treatment

Based on incidence and severity of adverse events

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

Secondary Outcome Measures

Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment

Objective response rate (ORR)

Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment

Progression free survival (PFS)

Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment

Overall survival (OS)

Full Information

NCT ID

NCT04745403

First Posted

January 25, 2021

Last Updated

June 27, 2022

Sponsor

Lion TCR Pte. Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT04745403

Brief Title

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

Acronym

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)

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Recruiting

Study Start Date

May 20, 2022 (Actual)

Primary Completion Date

July 1, 2023 (Anticipated)

Study Completion Date

July 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Lion TCR Pte. Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatocellular Carcinoma

Keywords

Hepatitis B virus, Hepatocellular Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

mRNA HBV/TCR T-cells

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

mRNA HBV/TCR T-cells

Intervention Description

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.

Primary Outcome Measure Information:

Title

Safety evaluation of mRNA HBV/TCR T-cell treatment

Description

Based on incidence and severity of adverse events

Time Frame

Start of treatment until 28 days post last dose

Title

Analysis of modifications of tumour microenvironment caused by mRNA HBV/TCR T-cell treatment

Description

Histological staining using biopsy and analysis of serum factors such as cytokines and chemokines

Time Frame

Start of treatment until end of study

Secondary Outcome Measure Information:

Title

Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment

Description

Objective response rate (ORR)

Time Frame

Up to 4 years

Title

Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment

Description

Progression free survival (PFS)

Time Frame

Up to 4 years

Title

Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment

Description

Overall survival (OS)

Time Frame

Up to 4 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Royce Fam

Phone

69260818

royce.fam@liontcr.com

Facility Information:

Facility Name

Singapore General Hospital

City

Singapore

ZIP/Postal Code

169608

Country

Singapore

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Thinesh L Krishnamoorthy

Phone

62223322

thinesh.l.krishnamoorthy@singhealth.com.sg

Ext

Krishnamoorthy

thinesh.l.krishnamoorthy@singhealth.com.sg

First Name & Middle Initial & Last Name & Degree

Thinesh L Krishnamoorthy

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

23941866

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 virus. Mol Ther Nucleic Acids. 2013 Aug 13;2(8):e114. doi: 10.1038/mtna.2013.43.

Results Reference

result

PubMed Identifier

28737510

Citation

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.

Results Reference

result

PubMed Identifier

30711630

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 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.

Results Reference

result

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

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