Hepatocellular Carcinoma
Conditions
Keywords
Hepatitis B virus, Hepatocellular Carcinoma
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.
Interventions
DRUGmRNA 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.
Sponsors
Lion TCR Pte. Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety evaluation of mRNA HBV/TCR T-cell treatment | Start of treatment until 28 days post last dose | Based on incidence and severity of adverse events |
| Analysis of modifications of tumour microenvironment caused by mRNA HBV/TCR T-cell treatment | Start of treatment until end of study | Histological staining using biopsy and analysis of serum factors such as cytokines and chemokines |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment | Up to 4 years | Objective response rate (ORR) |
Countries
Singapore
Contacts
Primary ContactRoyce Fam
Outcome results
None listed