TCR-Redirected T Cell Treatment in Patients With Recurrent HBV-related Hepatocellular Carcinoma Post Liver Transplantation

Phase I Study of T Cell Receptor-Redirected T Cells With Recurrent HBV Treatment in Patients-Related Hepatocellular Carcinoma in Post Liver Transplantation

This is a single-arm and open-label study to assess the safety, tolerability and primary efficacy of the HBV specific T cell receptor (HBV/TCR) redirected T cell in patients with recurrent Hepatitis B virus (HBV) related hepatocellular carcinoma post liver transplantation.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Diagnosis as hepatocellular carcinoma (HCC).
2. Recurrent locally advanced and/or metastatic hepatocellular carcinoma (HCC) post liver transplantation.
3. Seropositive for hepatitis B surface antigen, or presence of HBV DNA or HBV RNA.
4. HLA profile matching with HLA-class I restriction element of the available T cell receptors.
5. ECOG performance status ≤ 2.

6. Laboratory criteria:

   1. Liver function: ALT and AST ≤ 5 of upper limit of normal (ULN), TBIL ≤ 3 x ULN.
   2. Neutrophil cell number ≥1.5×10^9/L.
   3. Platelet count ≥100×10^9/L.
7. Ability to provide informed consent.
8. Willing and able to comply with all study procedures.

Exclusion Criteria:

1. Second primary malignancy that is clinically detectable at the time of consideration for study enrolment.
2. Likelihood to require steroid treatment during the period of the clinical trial.
3. Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples.
4. Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
5. Administration of any other cell therapy, including NK, CIK, DC, CTL, CAR- T, stem cells or combined therapy of the kind within 28 days prior to start of treatment.
6. 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: 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; Autologous T cells with HBV antigen-specific TCR	Biological: TCR-T cells; Patients will receive 1 x 10^4 cells/kg to 5 x 10^6 cells/kg bodyweight of TCR redirected T cells by IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety evaluation of the TCR-T treatment	Incidence of adverse events/serious adverse events	Start of Treatment until 28 days post last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	Tumour assessment will be according to RECIST v1.1. This is based on percentage of participants with Complete Response (CR) and Partial Response (PR) according to RECIST v1.1 from baseline.	Start of treatment until disease progression, and subsequent follow up up to 24 months post treatment.
Progression-free survival (PFS)	1-year PFS is measured by the number of patients with stable disease after 1 year, using RECIST v1.1.	Start of treatment until disease progression, and at 6-month and 1-year.
Overall survival (OS)	OS is defined as the time from randomisation until death by any cause. Participants will be followed up for survival follow up for two years.	Start of treatment until disease progression, and at 6-month and 1-year.

Collaborators and Investigators

• Sponsor: Xiaoshun He
• Collaborators: Lion TCR Pte. Ltd.

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.
• Tan AT, Yang N, Lee Krishnamoorthy T, Oei V, Chua A, Zhao X, Tan HS, Chia A, Le Bert N, Low D, Tan HK, Kumar R, Irani FG, Ho ZZ, Zhang Q, Guccione E, Wai LE, Koh S, Hwang W, Chow WC, Bertoletti A. Use of Expression Profiles of HBV-DNA Integrated Into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy. Gastroenterology. 2019 May;156(6):1862-1876.e9. doi: 10.1053/j.gastro.2019.01.251. Epub 2019 Jan 31.

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2018
• Primary Completion (Actual): February 18, 2020
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: December 16, 2020
• First Submitted That Met QC Criteria: December 16, 2020
• First Posted (Actual): December 21, 2020

Study Record Updates

• Last Update Posted (Actual): December 21, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: December 1, 2020

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-2-2

Drug and device information, study documents

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