Results of the first-in-human study of ABBV-075 (mivebresib), a pan-inhibitor of bromodomain (BD) and extra terminal (BET) proteins, in patients (pts) with relapsed/refractory (R/R) solid tumors.

2510Background: BDs are protein domains that bind to acetylated histone tails, leading to upregulation of target genes driving oncogenesis. Inhibition of the BET family prevents assembly of the macromolecular complex and its transcriptional response. ABBV-075 is a pan-BET inhibitor that induces death in cell lines and tumor growth inhibition in xenograft models. This first-in-human, phase 1, two-part study (NCT02391480) assessed the safety and pharmacokinetics of ABBV-075 in pts with advanced tumors. Results from the dose escalation part in pts with solid tumors are reported. Methods: The dose escalation part of this open-label study enrolled adult pts with R/R solid tumors in a 3+3 fashion. Endpoints included maximum tolerated dose, recommended phase 2 dose (RP2D) at different ABBV-075 dosing schedules (daily, Monday/Wednesday/Friday [MWF], or 4 days on/3 off [4/7]), safety and preliminary efficacy. Results: As of Dec 2017, 72 pts with solid tumors enrolled in the dose escalation cohort. Most common tumo...