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

NCT04677088 | Unknown Phase 1

• 1 other identifier: LTCR-HCC-2-2
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Recurrent Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Safety evaluation of the TCR-T treatment

  Incidence of adverse events/serious adverse events

  Start of Treatment until 28 days post last dose

Secondary Outcomes (3)

• Overall Response Rate

  Start of treatment until disease progression, and subsequent follow up up to 24 months post treatment.

• Progression-free survival (PFS)

  Start of treatment until disease progression, and at 6-month and 1-year.

• Overall survival (OS)

  Start of treatment until disease progression, and at 6-month and 1-year.

Study Arms (1)

HBV/ TCR T cell infusion

EXPERIMENTAL

Autologous T cells with HBV antigen-specific TCR

Biological: TCR-T cells

Interventions

TCR-T cells BIOLOGICAL

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.

HBV/ TCR T cell infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis as hepatocellular carcinoma (HCC).
• Recurrent locally advanced and/or metastatic hepatocellular carcinoma (HCC) post liver transplantation.
• Seropositive for hepatitis B surface antigen, or presence of HBV DNA or HBV RNA.
• HLA profile matching with HLA-class I restriction element of the available T cell receptors.
• ECOG performance status ≤ 2.
• Laboratory criteria:
• Liver function: ALT and AST ≤ 5 of upper limit of normal (ULN), TBIL ≤ 3 x ULN.
• Neutrophil cell number ≥1.5×10\^9/L.
• Platelet count ≥100×10\^9/L.
• Ability to provide informed consent.
• Willing and able to comply with all study procedures.

You may not qualify if:

• 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.
• Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
• 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.
• Any condition that is unstable or which could jeopardise the safety of the patient and his/her compliance in the study.

Sponsors & Collaborators

• Xiaoshun He: lead
• Lion TCR Pte. Ltd.: collaborator

Study Sites (1)

The First Affiliated Hospital of Sun-Yat Sen University

Guangzhou, Guangdong, 510080, China

Location

Related Publications (4)

• 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.

  PMID: 30711630 BACKGROUND

• 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.

  PMID: 25308176 BACKGROUND

• 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.

  PMID: 21145860 BACKGROUND

• 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.

  PMID: 23941866 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD.

Study Record Dates

• First Submitted: December 16, 2020
• First Posted: December 21, 2020
• Study Start: March 29, 2018
• Primary Completion: February 18, 2020
• Study Completion: December 1, 2021
• Last Updated: December 21, 2020

Record last verified: 2020-12

Locations

CN (1)