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

Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02686372
• Other study ID #: LTCR-HCC-1-1
• Status: Completed
• Phase: Phase 1
• Start date: May 16, 2018
• Est. completion date: September 28, 2021

Study information

• Verified date: June 2022
• Source: Lion TCR Pte. Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: September 28, 2021
• Est. primary completion date: September 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Recurrence

Intervention

Biological:
• TCR-T
Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR
• No intervention and TCR-T (at crossover)
Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR

Locations

Country	Name	City	State
China	The First Affiliated Hospital, Sun-Yat Sen University	Guangzhou	Guangdong

Sponsors (3)

Lead Sponsor	Collaborator
Lion TCR Pte. Ltd.	First Affiliated Hospital, Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Country where clinical trial is conducted

China, 

References & Publications (3)

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. — View Citation

Koh S, Shimasaki N, Suwanarusk R, Ho ZZ, Chia A, Banu N, Howland SW, Ong AS, Gehring AJ, Stauss H, Renia L, Sällberg 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:e114. doi: 10.1038/mtna.2013.43. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	To evaluate objective response rate	ORR	Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first)