Current results of a phase I study of DKN-01 in combination with paclitaxel (P) in patients (pts) with advanced DKK1+ esophageal cancer (EC) or gas...

Date 29 June 2016
Event ESMO World Congress on Gastrointestinal Cancer 2016
Session ESMO World Congress on Gastrointestinal Cancer 2016 - Abstracts book
Presenter D.P. Ryan
Citation Annals of Oncology (2016) 27 (2): 102-117. 10.1093/annonc/mdw200
Authors D.P. Ryan1, J. Murphy1, D. Mahalingam2, J. Strickler3, S. Stein4, C. Sirard5, S. Landau6, J. Bendell7
  • 1Massachusetts General Hospital, Boston, Massachusetts, USA, /
  • 2Univ. of Texas Health Sciences Center San Antonio, San Antonio, Texas, USA, /
  • 3Duke University, Durham, North Carolina, USA, /
  • 4Yale University Cancer Center, New Haven, Connecticut, USA, /
  • 5Leap Therapeutics, Cambridge, Massachusetts, USA, /
  • 6Health Care Ventures, Cambridge, Massachusetts, USA, /
  • 7Sarah Cannon Research Institute and Tennessee Oncology, Nashville, Tennessee, USA, /

Abstract

DKK1 is important for canonical Wnt signaling and directly activates non-canonical Wnt signaling through pathways such as Rho and JNK. High DKK1 tissue concentrations in EC correlate with shorter overall survival (OS); increased activity of non-canonical signaling by DKK1 may be a reason for shortened OS. Targeting Wnt signaling pathways experimentally have led to modulation of cancer-related immunotherapy. DKN-01 (D) is a humanized monoclonal antibody recognizing DKK1 with preliminary safety and efficacy demonstrated in this study's dose escalation phase in pts with EC or GEJ at the MTD (300 mg) of D in combination with P. We continue to evaluate safety and efficacy of D in combination with P in pts with EC and GEJ cancer in multiple dose confirmation phases.