presentation tonight, page-5

By the way the abstract of the presentation is here :
"NOVEL HEPARANASE INHIBITOR PI-88 EXTENDS DISEASE FREE SURVIVAL IN A RANDOMIZED PHASE II ADJUVANT CLINICAL TRIAL IN PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC) AFTER CURATIVE RESECTION


P.J. Chen 1, P.H. Lee 2, D.Y. Lin 3, C.C. Wu 4, L.B. Jeng 5, P.W. Lin 6, K.T. Mok 7, A.M. Gautam 8, J.R. Zalcberg 9

1 Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 2 Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan; 3 Internal Medicine, Chang Gung Memorial Hospital-Linkou Medical Centre and Chang Gung University, Taipei, Taiwan; 4 Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan; 5 Department of Surgery, China Medical University Hospital, Taichung, Taiwan; 6 Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan; 7 Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 8 Progen Industries Limited, Brisbane, Australia; 9 Department of Haematology and Medical Oncology, Peter MacCallum Cancer Institute, Melbourne, Australia


Background and Aims: PI-88 is a first in class mimetic of heparan sulfate (HS), an antagonist of HS interaction with angiogenic growth factors and an inhibitor of HS cleavage of basement membrane by heparanase. This novel product is being developed to target angiogenesis and metastasis; two biological processes that are important factors involved in postoperative recurrence of HCC. Primary objective of the clinical trial was to evaluate the efficacy of PI-88 in patients with HCC following curative resection. Method: In total, 172 patients (168 evaluable, male:female = 133:35, median age = 53 years) were recruited in a multi-center phase II clinical trial. Eligible patients had primary HCC suitable for curative resection, and ECOG score =2. Eligible patients were randomized 1:1:1 to an untreated control arm (A), or to self-administer subcutaneously either 160 (B) or 250 mg/day (C) PI-88 for 4 consecutive days per week for 3 weeks per 4 week cycle (approximately 57 pts per arm). Patients in arms B and C received up to 9 treatment cycles (36 wks), with a follow-up period of 12 weeks and patients in arm A were followed up for 48 weeks. Primary endpoint was defined as disease free rate (DFR) and secondary endpoints were disease free survival (DFS) and safety. DFR, DFS and safety were evaluated in a preliminary assessment at 30 wks. Results: Preliminary data analysis at 30 wks indicated that DFR was A:B:C (%) = 64.9:79.2:71, with patients outcomes in arms A:B:C = 20:11:12 patients recurred, 37:42:30 disease free and 1:3:12 dropped out. Dropouts in arms A:B:C were 7 patients due to slow recovery from Grade 3 elevation of ALT (0:1:6), 3 withdrew consent (1:2:0), 2 with =Grade 2 thrombocytopenia (0:0:2), 3 with adverse events (0:0:3) and 1 due to excluded concomitant drug (0:0:1). DFS at 30 weeks improved by 76% at the 80th percentile in 160 mg/day arm compared to control (from 17 weeks to 30 weeks). Conclusions: Preliminary data analysis demonstrates that PI-88 appears efficacious in prolonging DFS in patients with post-resection HCC. Complete 48 weeks data analysis will be presented for all patients.
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