Open AccessDevelopment of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies
Author(s) -
Gerald S. Falchook,
Seth Rosen,
Patricia LoRusso,
Justin M. Watts,
Shilpa Gupta,
Catherine C. Coombs,
Moshe Talpaz,
Razelle Kurzrock,
Monica Mita,
Ryan D. Cassaday,
Wael A. Harb,
Julio Antonio Peguero,
David C. Smith,
Sarina A. Piha-Paul,
Russell Z. Szmulewitz,
Marcus Smith Noel,
Swamy Yeleswaram,
Phillip Liu,
Julie Switzky,
Gongfu Zhou,
Fred Zheng,
Amitkumar Mehta
Publication year - 2020
Publication title -
clinical cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.427
H-Index - 324
eISSN - 1557-3265
pISSN - 1078-0432
DOI - 10.1158/1078-0432.ccr-18-4071
Subject(s) - tolerability , bromodomain , pharmacodynamics , medicine , pharmacokinetics , nausea , adverse effect , pharmacology , oncology , epigenetics , biology , biochemistry , gene
Bromodomain and extraterminal (BET) proteins are key epigenetic transcriptional regulators, inhibition of which may suppress oncogene expression. We report results from 2 independent first-in-human phase 1/2 dose-escalation and expansion, safety and tolerability studies of BET inhibitors INCB054329 (study INCB 54329-101; NCT02431260) and INCB057643 (study INCB 57643-101; NCT02711137).