454O - A randomized phase III study of napabucasin [BBI608] (NAPA) vs placebo (PBO) in patients (pts) with pretreated advanced colorectal cancer (ACRC): t...

Date 09 October 2016
Event ESMO 2016 Congress
Session Gastrointestinal tumours, colorectal 1
Topics Colon and Rectal Cancer
Presenter Derek Jonker
Citation Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370
Authors D.J. Jonker1, L. Nott2, T. Yoshino3, S. Gill4, J. Shapiro5, A. Ohtsu6, J. Zalcberg7, M.M. Vickers8, A. Wei9, Y. Gao10, N. Tebbutt11, B. Markman12, T. Esaki13, S. Koski14, M. Hitron10, N.M. Magoski15, J. Simes16, C. Li17, D. Tu18, C.J. O'Callaghan19
  • 1Department Of Medicine, Division Of Medical Oncology, Ottawa Hospital Research Institute, University of Ottawa, K1H8L6 - Ottawa/CA
  • 2Medical Oncology, Royal Hobart Hospital, Hobart/AU
  • 3Gastroenterology & Gastrointestinal Oncology, National Cancer Center Hospital East, 277-8577 - Chiba/JP
  • 4Department Of Medicine, Vancouver General Hospital & HSC, British Columbia University, Vancouver/CA
  • 5Department Of Medicine, Cabrini Hospital, Melbourne/AU
  • 6Department Of Gastroenterology And Gastrointestinal Oncology, National Cancer Center East, 277-8577 - Kashiwa/JP
  • 7School Of Public Health & Preventive Medicine, Monash University, Melbourne/AU
  • 8Department Of Medicine, Division Of Medical Oncology, Ottawa Hospital Research Institute, University of Ottawa, Ottawa/CA
  • 9Division Of General Surgery, Princess Margaret Cancer Centre, University of Toronto, Toronto/CA
  • 10Clinical Development, Boston Biomedical Incorporated, Boston/US
  • 11Medical Oncology, Austin Hospital, 3084 - Heidelberg/AU
  • 12Monash Cancer Centre, Monash Health, 3165 - Melbourne/AU
  • 13Gastrointestinal And Medical Oncology, National Kyushu Cancer Center, 811-1395 - Fukuoka/JP
  • 14Department Of Medicine, University of Alberta Cross Cancer Institute, Edmonton/CA
  • 15Canadian Cancer Trials Group, Queens University, Kingston/CA
  • 16Oncology, NHMRC Clinical Trials Centre, Sydney/AU
  • 17Global Oncology, Boston Biomedical Incorporated, Boston/US
  • 18Department Of Mathematics And Statistics, Canadian Cancer Trials Group, Queens University, Kingston/CA
  • 19Department Of Public Health Sciences, Canadian Cancer Trials Group, Queens University, Kingston/CA



NAPA is a first-in-class cancer stemness inhibitor that targets STAT3, with promising activity in early trials.


Pts with ACRC who had failed all available standard therapy were randomized 1:1 to NAPA 480mg po q12h or PBO. Primary endpoint was overall survival (OS). Pre-specified biomarker analyses included pSTAT3 positivity by IHC in archival tissue based on nuclear staining of cancer cells >5% and stroma ≥2+. The study, designed to enrol 650 pts, was stopped after a futility analysis on disease control rate (DCR) in the first 96 pts. Analyses included Intent-to-treat (ITT) and exploratory Pre-defined Minimum Effective Treatment (pts who received ≥50% total daily dose for ≥6.4 weeks).


282 pts were randomized (138 NAPA, 144 PBO) from 04/2013 - 05/2014 when the trial was unblinded, accrual closed, and protocol treatment stopped after the futility analysis. Pts were median age = 64 (32 to 85); male = 65%; ECOG 0:1 (%) =28:72; >4 prior regimens = 98%; prior anti-VEGF = 89%; KRAS WT = 52%. No significant difference was observed in OS, progression free survival (PFS) or DCR between NAPA and PBO in the ITT analysis. AE more frequent with NAPA included: any grade diarrhea (88 vs 32%), nausea (63 vs 47%), and anorexia (56 vs 46%), all p 


In this trial, NAPA monotherapy did not improve OS or PFS in unselected ACRC. While pSTAT3 positivity was a poor prognostic factor in untreated pts, NAPA treatment in pts with positive pSTAT3 significantly improved OS.

Clinical trial identification


Legal entity responsible for the study

Canadian Cancer Trials Group (CCTG) at Queens University in Kingston, ON, Canada


Canadian Cancer Society Research Institute (CCSRI) with funding support from Boston Biomedical Inc.


D.J. Jonker: Co-investigator on trials sponsored by Boston Biomedical Incorporated. No direct or indirect financial or other gain. No personal conflict. L. Nott: No conflict of interest pertaining to this research. Member on advisory committees for Roche and MSD. T. Yoshino: No conflict of interest relevant to this research. Has received research funding from GlaxoSmithKline K.K., and Boehringer Ingelheim GmbH. J. Zalcberg: No relevant conflicts for this research. Research and Travel Support Bayer (Stivarga) M.M. Vickers: No relevant conflicts for this research. Advisory Boards for Ipsen, Celgene, Amgen. Y. Gao: Employee, Boston Biomedical Incorporated T. Esaki: Research Funding; Sumitomo Dainippon Pharma. M. Hitron, C. Li: Employee, Boston Biomedical Incorporated. All other authors have declared no conflicts of interest.