A Study of TCR-Redirected T Cell Infusion in Subject With Recurrent HBV-related HCC Post Liver Transplantation

• ClinicalTrials.gov Identifier: NCT02719782
• Recruitment Status: Unknown
• First Posted: March 25, 2016
• Last Update Posted: November 16, 2018
• Sponsor: Lion TCR Pte. Ltd.
• Collaborators: Agency for Science, Technology and Research; Third Affiliated Hospital, Sun Yat-Sen University
• Information provided by (Responsible Party): Lion TCR Pte. Ltd.

Study Description

Brief Summary:

Hepatocellular carcinoma (HCC) recurrence rate is high among liver transplant patients, while treatment measures are limited. This study plans to recruit 10 patients with Hepatitis B virus (HBV) related HCC who underwent liver transplantation and are confirmed to have recurrent HCC. 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.

Condition or disease	Intervention/treatment	Phase
Recurrent Hepatocellular Carcinoma	Biological: Biological: TCR-T	Phase 1

Detailed Description:

This is a phase I, single armed and open labelled trial in patients with recurrent HBV related HCC after liver transplantation. Subjects who meet eligibility criteria will receive escalating doses of HBV specific T cell receptor (TCR-T) on Day 1, Day 8, Day 15 and Day 22 of the first 28-day treatment cycle, followed by every 2-week dosing on Day 1, Day 15, Day 29 and Day 43 of repeated cycle. A 21-day treatment break will be given between each cycle. Treatment will be continued until disease progression unless otherwise specified per investigator's discretion. Subjects will be followed up post treatment for safety monitoring, including monthly follow up for the first three month and every 2-monthly follow up up to 24 months post treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Study T Cell Receptor-Redirected T Cells Infusions in Subjects With Recurrent HBV-Related Hepatocellular Carcinoma in Post Liver Transplantation
• Actual Study Start Date: July 2, 2015
• Estimated Primary Completion Date: May 2019
• Estimated Study Completion Date: December 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: HBV/TCR T cell Infusion; This is a single-arm study. Patients will receive a total of 2 cycles, in which first 28-day treatment cycle consists of escalating doses of TCR-T on Day 1, Day 8, Day 15 and Day 22, followed by every 2-week dosing on Day 1, Day 15, Day 29 and Day 43 of second (final) cycle. A one month treatment break will be given between the cycles.	Biological: Biological: TCR-T; Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR

Outcome Measures

Primary Outcome Measures :

1. Safety of the TCR-T treatment [ Time Frame: Start of treament until 1 month after last treatment ]

Secondary Outcome Measures :

1. Efficacy of induction of tumor specific T cell responses as measured by the persistence of HBV specific T cells in peripheral blood samples at several time points following adoptive transfer [ Time Frame: Start of treatment until disease progression, and subsequent follow up up to 24 months post treatment ]
2. Systemic release of inflammatory cytokines after administration of transduced T cells compared to baseline [ Time Frame: Start of treatment until disease progression, and subsequent follow up up to 24 months post treatment ]

Other Outcome Measures:

1. 1-year PFS (progression free survival) which is measured by the number of patients with stable disease after 1 year, using mRECIST [ Time Frame: Start of treatment until disease progression, median 6 months ]

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosis as hepatocellular carcinoma (HCC)
• Underwent liver transplantation and confirmed recurrent HCC post operation
• Seropositive for hepatitis B surface antigen
• No major post-operative complication
• Life expectancy of at least 12 weeks
• Ability to provide informed consent
• Ability to comply with study procedures
• HLA profile matching with HLA-class I restriction element of the available T cell receptors

Exclusion Criteria:

• Administration of any other cell therapy, including NK, CIK, DC, CTL, CAR-T, stem cells or combined therapy of the kind within 3 months prior to enrolment
• Second primary malignancy that is clinically detectable at the time of consideration for study enrolment
• Likelihood to require steroid treatment during the period of the clinical trial
• Any other concurrent liver infections such as hepatitis A, C or D infection
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
• Known Central Nervous System tumours including metastatic brain disease.
• Any condition that is unstable or which could jeopardise the safety of the patient and his/her compliance in the study
• Patients with reproductive potential who tested positive for serum or urine pregnancy test result within 14 days prior to enrolment.

Contacts and Locations

Contacts

Contact: Grace Khoo Koay; (65) 69260818; clinicaltrials@liontcr.com

Contact: Xiaofang Zheng; 86-(020)-8217-9791

Locations

China, Guangdong

Third Affiliated Hospital of Sun Yat-sen University; Recruiting

Guangzhou, Guangdong, China, 510630

Contact: Qi Zhang, Ph.D, MD (86)20-85253106

Sponsors and Collaborators

Lion TCR Pte. Ltd.

Agency for Science, Technology and Research

Third Affiliated Hospital, Sun Yat-Sen University

Investigators

• Principal Investigator: Qi Zhang, MD; Third Affiliated Hospital, Sun Yat-Sen University
• Study Chair: Antonio Bertoletti, MD; Duke-NUS Graduate Medical School

More Information

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.

• Responsible Party: Lion TCR Pte. Ltd.
• ClinicalTrials.gov Identifier: NCT02719782
• Other Study ID Numbers: LTCR-HCC-2-1
• First Posted: March 25, 2016
• Last Update Posted: November 16, 2018
• Last Verified: November 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Hepatocellular; Recurrence; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Pathologic Processes; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases