624PD - A phase III trial of muparfostat (PI-88) as adjuvant therapy in patients with hepatitis virus related hepatocellular carcinoma (HV-HCC) after resec...

Date 11 September 2017
Event ESMO 2017 Congress
Session Gastrointestinal tumours, non-colorectal
Topics Drug Development
Hepatobiliary Cancers
Cancer in Special Situations
Gastrointestinal Cancers
Citation Annals of Oncology (2017) 28 (suppl_5): v209-v268. 10.1093/annonc/mdx369
Authors P. Chen1, P. Lee2, K. Han3, J. Fan4, T.T. Cheung5, R. Hu6, S.W. Paik7, W. Lee8, G. Chau9, L. Jeng10, H.J. Wang11, J.Y. Choi12, C. Chen13, M. Cho14, M. Ho15, C. Wu16, K.S. Lee17, Y. Mao18, F. Hu19, K. Lai20
  • 1Graduate Institute Of Clinical Medicine And Department Of Medical Research, National Taiwan University and National Taiwan University Hospital, 100 - Taipei/TW
  • 2Department Of Surgery, National Taiwan University Hospital, 100 - Taipei/TW
  • 3Department Of Internal Medicine, Yonsei University College of Medicine, Seoul/KR
  • 4Liver Cancer Institute, Zhongshan Hospital, Cancer Center, Institute of Biomedical Sciences, Fudan University, Shanghai/CN
  • 5Department Of Surgery, Queen Mary Hospital and University of Hong Kong, Hong Kong/HK
  • 6Department Of Surgery, College Of Medicine, National Taiwan University Hospital, 100 - Taipei/TW
  • 7Department Of Gastroenterology, Samsung Medical Center, College of Medicine, Sungkyunkwan University, Seoul/KR
  • 8Division Of Liver And Transplantation Surgery, Department Of General Surgery, Chang Gung Memorial Hospital Linkou Branch, College of Medicine, Chang Gung University, Taipei/TW
  • 9Department Of General Surgery, Taipei Veterans General Hospital, Taipei/TW
  • 10Organ Transplantation Center, China Medical University Hospital, Taichung/TW
  • 11Department Of Surgery, College of Medicine, Ajou University, Seoul/KR
  • 12Division Of Hepatology, Department Of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul/KR
  • 13Liver Transplantation Center And Department Of Surgery, Chang Gung Memorial Hospital Kaohsiung Branch, College of Medicine, Chang Gung University, Kaohsiung/TW
  • 14Department Of Gastroenterology, Pusan National University Yangsan Hospital, Pusan/KR
  • 15Department Of Surgery, National Taiwan University Hospital, College of Medicine, National Taiwan University, 100 - Taipei/TW
  • 16Department Of General Surgery, Taichung Veterans General Hospital, Taichung/TW
  • 17Department Of Gastroenterology, Gangnam Severance Hospital, Seoul/KR
  • 18Department Of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing/CN
  • 19Graduate Institute Of Clinical Medicine, College of Medicine, National Taiwan University, Taipei/TW
  • 20New Drug Development, Medigen Biotechnology Corporation, Taipei/TW

Abstract

Background

Muparfostat is an investigational new drug which deters tumor growth by blocking tumor angiogenesis and prevents tumor cells from spreading via heparanase inhibition. Previous phase II trial of muparfostat demonstrated good tolerability and favorable clinical response.

Methods

This international multicenter clinical trial was conducted in Asia-Pacific region (Taiwan, Korea, China, and Hong-Kong) from 2011. A total of 520 HV-HCC patients after surgical resection were randomized (1:1) to receive injection of either muparfostat (160 mg/day, 4-days-on/3-days-off, 3-weeks-on/1-week-off) or placebo for 52 weeks and followed up for 96 weeks. The primary endpoint was centrally assessed disease-free survival (DFS). Secondary endpoints included overall survival (OS), time to recurrence, and safety.

Results

Baseline patient demographics and characteristics were balanced between the treatment and placebo arms. All subjects completed the 52-week treatment. After interim analysis in 2014, the trial was concluded in 2015. The final intention-to-treat analysis (N = 519) yielded a non-significant result (p > 0.05) on DFS, not reaching the primary end point. Nevertheless, per-protocol analysis (N = 423) revealed a possible positive protective effect in subgroup patients with microvascular invasion. Muparfostat showed a significant prolongation in the disease-free time after completion of the 1-year treatment (hazard ratio: 0.13, 95% CI: 0.017 - 0.991, p = 0.049). Muparfostat had a good safety profile. There were five clinically suspected cases of heparin-induced thrombocytopenia but only one was confirmed.

Conclusions

Despite the DFS was not improved in the overall treatment group, muparfostat could significantly prolong the DFS in the microvascular-invasion subgroup, comprising 40% of the trial population. The finding potentiated muparfostat as single therapy or in combination with other anti-cancer agents for future HCC adjuvant therapy trials.

Clinical trial identification

PATRON/NCT01402908

Legal entity responsible for the study

Medigen Biotechnology Corporation

Funding

Medigen Biotechnology Corporation

Disclosure

P-J. Chen: Honorarium from Medigen Biotechnology Corporation. K-L. Lai: Employee of Medigen Biotechnology Corporation. All other authors have declared no conflicts of interest.