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

A Phase I Study T Cell Receptor-Redirected T Cells Infusions in Subjects With Recurrent HBV-Related Hepatocellular Carcinoma in Post Liver Transplantation

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.

Study Overview

• Status: Unknown
• Conditions: Recurrent Hepatocellular Carcinoma
• Intervention / Treatment: Biological: Biological: TCR-T

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 Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510630
      • Recruiting
      • Third Affiliated Hospital of Sun Yat-sen University
      • Contact: Qi Zhang, Ph.D, MD; Phone Number: (86)20-85253106

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety of the TCR-T treatment	Start of treament until 1 month after last treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
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	Start of treatment until disease progression, and subsequent follow up up to 24 months post treatment
Systemic release of inflammatory cytokines after administration of transduced T cells compared to baseline	Start of treatment until disease progression, and subsequent follow up up to 24 months post treatment

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Lion TCR Pte. Ltd.
• Collaborators: Third Affiliated Hospital, Sun Yat-Sen University; Agency for Science, Technology and Research
• Investigators: Principal Investigator: Qi Zhang, MD, Third Affiliated Hospital, Sun Yat-Sen University; Study Chair: Antonio Bertoletti, MD, Duke-NUS Graduate Medical School

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): July 2, 2015
• Primary Completion (Anticipated): May 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: March 21, 2016
• First Submitted That Met QC Criteria: March 21, 2016
• First Posted (Estimate): March 25, 2016

Study Record Updates

• Last Update Posted (Actual): November 16, 2018
• Last Update Submitted That Met QC Criteria: November 15, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• 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-2-1

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