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
Sponsored by
About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Hepatitis B virus, Hepatocellular Carcinoma
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
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
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
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
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
No
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
Email
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
Email
thinesh.l.krishnamoorthy@singhealth.com.sg
Ext
Krishnamoorthy
Email
thinesh.l.krishnamoorthy@singhealth.com.sg
First Name & Middle Initial & Last Name & Degree
Thinesh L Krishnamoorthy
12. IPD Sharing Statement
Plan to Share IPD
No
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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