CELL INTELLIGENCE · 肿瘤细胞治疗研究

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

主要终点：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；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
次要终点：Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment；Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment；Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment

• mRNA HBV/TCR T-cells · EXPERIMENTAL · Escalating regime from 1x10e5 to 5-10x10e6 cells/kg bodyweight (BW) every 2 weeks.

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.