A Study of TCR-Redirected T Cell Infusion to Prevent Hepatocellular Carcinoma Recurrence Post Liver Transplantation

Lion TCR

Status and phase: Completed; Phase 1

Conditions: Hepatocellular Carcinoma

Treatments: Biological: No intervention and TCR-T (at crossover); Biological: TCR-T

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02686372

LTCR-HCC-1-1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 13 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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13 participants in 2 patient groups

HBV/TCR-T cell infusion

Experimental group

Description:

Subjects enrolled in the experimental (treatment) group will receive escalating doses of HBV/ TCR expressing autologous T cells. 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.

Treatment:

Biological: TCR-T

No intervention and TCR-T (at crossover)

Other group

Description:

No intervention and to be crossover to experimental arm upon confirmation of disease recurrence.

Treatment:

Biological: No intervention and TCR-T (at crossover)