Clinical trial NCT04677088: TCR-Redirected T Cell Treatment in Patients With Recurrent HBV-related Hepatocellular Carcinoma Post Liver Transplantation
Official title: Phase I Study of T Cell Receptor-Redirected T Cells With Recurrent HBV Treatment in Patients-Related Hepatocellular Carcinoma in Post Liver Transplantation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Recurrent Hepatocellular Carcinoma
Lead sponsor: First Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: Lion TCR Pte. Ltd.
First posted: 2020-12-21
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Safety evaluation of the TCR-T treatment
timeFrame: Start of Treatment until 28 days post last dose
Secondary outcomes:
measure: Overall Response Rate
timeFrame: Start of treatment until disease progression, and subsequent follow up up to 24 months post treatment.
measure: Progression-free survival (PFS)
timeFrame: Start of treatment until disease progression, and at 6-month and 1-year.
measure: Overall survival (OS)
timeFrame: Start of treatment until disease progression, and at 6-month and 1-year.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun-Yat Sen University
state: Guangdong
Study officials:
References:
citation: 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.
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.
citation: 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.
citation: 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.