Recurrent Hepatocellular Carcinoma
Conditions
Keywords
recurrent hepatocellular carcinoma, hepatitis B virus-related, post liver transplantation, HCC
Brief summary
Hepatocellular carcinoma (HCC) represent approximately 70-85% of liver cancer, in which Hepatitis B virus (HBV) is the major etiologic agent accounting for at least 80% of HCC in Asian countries. Overall, transplantation remains the best option however, HCC recurrence rate is high among liver transplant patients. While there are limited treatment measures for HBV-related HCC recurrences, the study hypothesized that LioCyx is capable of lysing target liver cells expressing the HBV cognate antigens and provide clinical benefit to patients with HBV-related HCC.
Detailed description
The study is a Phase I/II, open label, single-arm, multicenter study of LioCyx. Subjects with recurrent hepatitis B virus-related hepatocellular carcinoma who undergone liver transplantation will be enrolled. Approximately 6-12 subjects will be enrolled in Phase 1 dose regimen exploration, and approximately 60 subjects will be enrolled to characterize the safety and evaluate the efficacy of LioCyx All subjects will be followed up for survival until death.
Interventions
BIOLOGICALLioCyx
Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Recurrent locally advanced and/or metastatic hepatocellular carcinoma (HCC) post liver transplantation * Life expectancy of 3 months or greater * Have measurable disease by the revised response evaluation criteria in solid tumors (mRECIST) * History of positive test for hepatitis B virus surface antigen (HBsAg) * Expression of LioCyxTM target epitopes within specific human leukocyte antigen (HLA) class I profile * Had received treatment with at least one standard therapy or refused, appropriate approved therapy for their disease * 21 years of age or older * Eastern Cooperative Oncology Group (ECOG) performance status ≤1 * Willing and able to comply with all study procedures
Exclusion criteria
* Known, clinically suspected or has history of central nervous system (CNS) and bone metastasis * Tumor burden in the liver exceeding 70% * 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) * Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples * Women who are pregnant or breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety based on Incidence of Treatment-Emergent Adverse Events (AEs) and Serious AEs | Start of Treatment until 28 days post last dose | Review the safety profile of LioCyx by assessing the incidence of AEs and SAEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | Start of Treatment until first documented CR or PR, assessed up to 62 treatment weeks (protocol-defined treatment duration is until disease progression, death, or loss to follow up, whichever came first) | Tumor assessment will be according to mRECIST. This is based on percentage of participants with Complete Response (CR) and Partial Response (PR) according to mRECIST from baseline. |
| Overall Survival according to mRECIST | Start of Treatment until first protocol-defined PD, and survival follow up until death, assessed up to 62 treatment weeks (protocol-defined treatment duration is until disease progression, death, or loss to follow up, whichever came first) | Assess the efficacy following LioCyx in prolonging overall survival of patients in HBV-related HCC patients |
| Quality of life of patients | Baseline to 28 days post treatment (end of treatment) | Compare the quality of life of patients based on \[Functional Assessment of Chronic Illness Therapy- Hepatobiliary (FACIT-Hep), version 4\] |
Countries
China, Singapore
Outcome results
None listed