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

A Phase I Study of T Cell Receptor-Redirected T Cell Infusion For Prevention of Hepatocellular Carcinoma Recurrence in Subjects With Hepatitis B Virus-Related Hepatocellular Carcinoma Post Liver Transplantation

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.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Biological: TCR-T; Biological: No intervention and TCR-T (at crossover)

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital, Sun-Yat Sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HBV/TCR-T cell infusion; 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.	Biological: TCR-T; Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR
Other: No intervention and TCR-T (at crossover); No intervention and to be crossover to experimental arm upon confirmation of disease recurrence.	Biological: No intervention and TCR-T (at crossover); Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Evaluate safety of the TCR-T treatment	Measures include - assessments of Adverse Events (AEs) and Serious AEs,	Start of Treatment until 28 days post last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate Progression Free Survival rate	PFS	Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first)
To evaluate Duration of response rate	DOR	Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first)
To evaluate objective response rate	ORR	Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first)

Collaborators and Investigators

• Sponsor: Lion TCR Pte. Ltd.
• Collaborators: First Affiliated Hospital, Sun Yat-Sen University; Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Investigators: Principal Investigator: Xiaoshun He, MD, First Affiliated Hospital, Sun Yat-Sen University

Publications and helpful links

General Publications

• Qasim W, Brunetto M, Gehring AJ, Xue SA, Schurich A, Khakpoor A, Zhan H, Ciccorossi P, Gilmour K, Cavallone D, Moriconi F, Farzhenah F, Mazzoni A, Chan L, Morris E, Thrasher A, Maini MK, Bonino F, Stauss H, Bertoletti A. Immunotherapy of HCC metastases with autologous T cell receptor redirected T cells, targeting HBsAg in a liver transplant patient. J Hepatol. 2015 Feb;62(2):486-91. doi: 10.1016/j.jhep.2014.10.001. Epub 2014 Oct 13.
• Gehring AJ, Xue SA, Ho ZZ, Teoh D, Ruedl C, Chia A, Koh S, Lim SG, Maini MK, Stauss H, Bertoletti A. Engineering virus-specific T cells that target HBV infected hepatocytes and hepatocellular carcinoma cell lines. J Hepatol. 2011 Jul;55(1):103-10. doi: 10.1016/j.jhep.2010.10.025. Epub 2010 Nov 23.
• Koh S, Shimasaki N, Suwanarusk R, Ho ZZ, Chia A, Banu N, Howland SW, Ong AS, Gehring AJ, Stauss H, Renia L, Sallberg M, Campana D, Bertoletti A. A practical approach to immunotherapy of hepatocellular carcinoma using T cells redirected against hepatitis B virus. Mol Ther Nucleic Acids. 2013 Aug 13;2(8):e114. doi: 10.1038/mtna.2013.43.

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2018
• Primary Completion (Actual): September 28, 2021
• Study Completion (Actual): September 28, 2021

Study Registration Dates

• First Submitted: February 17, 2016
• First Submitted That Met QC Criteria: February 17, 2016
• First Posted (Estimate): February 19, 2016

Study Record Updates

• Last Update Posted (Actual): June 30, 2022
• Last Update Submitted That Met QC Criteria: June 27, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: HCC; hepatocellular carcinoma; hepatitis B virus-related; post liver transplantation
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Recurrence
• Other Study ID Numbers: LTCR-HCC-1-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No