Article Text

Download PDFPDF

273 Phase i study of LioCyx-M, autologous hepatitis B virus (HBV)-specific T cell receptor (TCR) T-cells, in recurrent HBV-related hepatocellular carcinoma (HCC) post-liver transplantation
Free
  1. Wenjie Chen1,
  2. Jintao Cheng1,
  3. Xiaofang Zheng1,
  4. Fan Yang1,
  5. Royce Fam2,
  6. Sarene Koh3,
  7. Lu-En Wai3,
  8. Tingting Wang2,
  9. Antonio Bertoletti4 and
  10. Qi Zhang1
  1. 13rd Aff Hospital, Sun Yat-Sen University, Guangzhou, China
  2. 2Lion TCR Pte Ltd, Singapore, Singapore
  3. 3Lion TCR Pte Ltd, A*STAR, Singapore, Singapore
  4. 4Lion TCR Pte Ltd,Duke-NUS Medical School, Singapore, Singapore
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint is the author/funder, who has granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.

  • Until the paper has been able to undergo proper copyediting, typesetting, and author proofing, readers should be aware that the specific preprint information below may contain errors and has not been finalized by authors.

Abstract

Background LioCyx-M is an immunotherapeutic product based on autologous T cells transiently modified with in vitro transcribed mRNA encoding HBV-specific T-cell receptors (TCR). We have previously shown, in a compassionate setting, the ability of LioCyx-M cells to recognize and lyse hepatocellular carcinoma (HCC) expressing HBV antigens derived from HBV-DNA integration in patients with HCC recurrence post-liver transplant.1 Here, we report our phase I study aimed to determine the feasibility, safety and preliminary efficacy of LioCyx-M in recurrent HBV-related HCC post-liver transplantation

Methods Eligible patients with HBsAg-positive recurrent HCC as well as HLA-matched to selected TCRs were enrolled in this study. All patients underwent leukapheresis prior to treatment and peripheral blood mononuclear cells (PBMC) were collected for LioCyx-M manufacturing. During the 1st treatment cycle, patients received 4 escalating doses of 1×104 cells/kg, 1×105 cells/kg, 1×106 cells/kg, 5×106 cells/kg bodyweight (BW) intravenously every 7 days. Adverse events were evaluated by Common Terminology Criteria for Adverse Events Version 4.0. In the second treatment cycle, one infusion of LioCyx-M at dose of 1–5 × 106 cells/kg BW was intravenously administrated every 7 days for 4 weeks. The anti-tumour efficacy of LioCyx-M was evaluated per RECIST 1.1 criteria and survival was followed-up during the study.

Results Six patients were enrolled, with a median age of 35.5 (range: 28 - 47). These patients received a median number of 6.5 doses of LioCyx-M therapy (range: 4 - 12). Only fever was observed as treatment-related AEs. Grade 1 fever was observed at dose levels of 1 × 104 cells/kg BW (n=1) and 1–5 × 106 cells/kg BW (n=3) respectively. No cytokine release syndrome- and neurotoxicity-like AEs were observed. Out of 4 patients evaluable for tumor response, the median of time to progression was at 1.3 months (range: 1.2 - 1.6 months). The median overall survival was 14 months (range: 4 - 22 months). At data cutoff (30 April 2020), one patient was still alive and 5 were deceased.

Conclusions Our data showed that multiple infusions of LioCyx-M are well tolerated at all dose levels administrated in recurrent HCC post liver transplantation, with no adverse effect to the transplanted liver. This calls for further assessment in a Phase 2 study.

Acknowledgements Funding: Lion TCR.

Trial Registration NCT02719782

Ethics Approval The study was approved by Sun Yat-Sen Third Affiliated Hospital’s Ethics Board, approval number [2015]2-157.

Reference

  1. Tan AT, Yang N, Lee Krishnamoorthy T, et al. Use of Expression Profiles of HBV-DNA Integrated Into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy. Gastroenterology 2019;156(6):1862–1876.e9.

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.