Cancer Chemotherapy and Pharmacology

, Volume 74, Issue 1, pp 125–130

Phase 1, open-label, dose-escalation, and pharmacokinetic study of STAT3 inhibitor OPB-31121 in subjects with advanced solid tumors


    • Sarah Cannon Research Institute/Tennessee OncologyPLLC
  • David S. Hong
    • MD Anderson Cancer Center
  • Howard A. BurrisIII
    • Sarah Cannon Research Institute/Tennessee OncologyPLLC
  • Aung Naing
    • MD Anderson Cancer Center
  • Suzanne F. Jones
    • Sarah Cannon Research Institute/Tennessee OncologyPLLC
  • Gerald Falchook
    • MD Anderson Cancer Center
  • Patricia Bricmont
    • Otsuka Pharmaceutical Development and Commercialization, Inc
  • Agnes Elekes
    • Otsuka Pharmaceutical Development and Commercialization, Inc
  • Edwin P. Rock
    • Otsuka Pharmaceutical Development and Commercialization, Inc
  • Razelle Kurzrock
    • MD Anderson Cancer Center
    • Center for Personalized Cancer TherapyUC San Diego Moores Cancer Center
Original Article

DOI: 10.1007/s00280-014-2480-2

Cite this article as:
Bendell, J.C., Hong, D.S., Burris, H.A. et al. Cancer Chemother Pharmacol (2014) 74: 125. doi:10.1007/s00280-014-2480-2



To determine the maximum tolerated dose (MTD) and biologic activity of OPB-31121, an oral inhibitor of STAT3, administered twice daily (BID) to subjects with advanced solid tumors.


.Subjects received escalating doses of OPB-31121 BID for the first 21 days of each 28-day cycle in a standard 3 + 3 design. Dose-limiting toxicities (DLTs), safety, pharmacokinetics, and antitumor activity were assessed.


Thirty subjects were treated twice daily with OPB-31121 at 6 dose levels: 50 mg (n = 4); 70 mg (n = 3); 140 mg (n = 3); 200 mg (n = 4); 300 mg (n = 9); 350 mg (n = 7). There were no DLTs observed until 300 mg BID (Grade 3 lactic acidosis). At the next dose level (350 mg BID), two subjects had DLTs (Grade 3 vomiting and Grade 3 diarrhea). Thus, 300 mg BID was declared the MTD. OPB-31121-related adverse events included nausea (80 %), vomiting (73 %), diarrhea (63 %), and fatigue (33 %), all of which were primarily grade 1/2. Pharmacokinetics demonstrated high inter-subject variability with exposures 146- to 4,788-fold lower than target concentrations from tumor-bearing mouse models. No objective responses were observed, and all subjects who completed two cycles of treatment had disease progression at their first assessment.


Twice-daily administration of OPB-31121 was feasible up to doses of 300 mg. The pharmacokinetic profile was unfavorable, and no objective responses were observed.


STAT3OPB-31121Dose escalationSolid tumors

Copyright information

© Springer-Verlag Berlin Heidelberg 2014