Hepatocellular Carcinoma
Conditions
Keywords
hepatocellular carcinoma, hepatitis B virus-related, post liver transplantation, HCC
Brief summary
Hepatocellular Carcinoma (HCC) recurrence rate is high among liver transplant patients, while treatment measures are limited. This study plans to recruit 39 subjects with Hepatitis B virus (HBV) related HCC after liver transplantation. The objective of the study is to assess the safety, tolerability and effectiveness of the HBV specific T cell receptor (HBV/TCR) redirected T cell in the target population.
Detailed description
A open-label, cohort clinical study of T cell receptor-redirected T cells to prevent recurrence of HBV-related hepatocellular carcinoma after liver transplantation. Subjects will be enrolled into the observation cohort or treatment cohort. Subjects enrolled in the treatment group will receive escalating doses of HBV/ TCR expressing autologous T cells after confirming eligibility. The interval between the first two doses is 14 days, followed by one month of safety monitoring, before subsequent two doses of 1 month interval in between. Thereafter, subjects would enter into observation period of the safety and tolerability of the treatment and will be followed up until disease relapse. Upon disease recurrence, eligible patient may receive HBV specific T-cell receptor (TCR-T) treatment.
Interventions
BIOLOGICALTCR-T
Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR
BIOLOGICALNo intervention and TCR-T (at crossover)
Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR
Sponsors
First Affiliated Hospital, Sun Yat-Sen University
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Lion TCR Pte. Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis as hepatocellular carcinoma (HCC) * Underwent liver transplantation * Seropositive for hepatitis B surface antigen (HBsAg), or presence of HBV DNA or HBV RNA before liver transplantation * Expression of TCR-T target epitopes within specific human leukocyte antigen (HLA) class I profile * No major post-operative complication * Life expectancy of at least 3 months * Ability to provide informed consent * Ability to comply with study procedures
Exclusion criteria
* Known, clinically suspected or has history or central nervous system (CNS) and bone metastasis * Significant ongoing immunologic rejection based on pathology and clinical diagnosis * Evidence or history of significant bleeding diathesis or coagulopathy * Prior exposure to any cell therapy such as, but not limited to NK, CIK, DC, CTL, stem cells therapy * Known history of testing positive for human immunodeficiency virus (HIV) 1 or 2 or known acquired immunodeficiency syndrome (AIDS) * Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection * Women who are pregnant or breast-feeding * Any condition that is unstable or which could jeopardise the safety of the patient and his/her compliance in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate safety of the TCR-T treatment | Start of Treatment until 28 days post last dose | Measures include \- assessments of Adverse Events (AEs) and Serious AEs, |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate Progression Free Survival rate | Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first) | PFS |
| To evaluate Duration of response rate | Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first) | DOR |
| To evaluate objective response rate | Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first) | ORR |
Countries
China
Outcome results
None listed