A phase I, open-label study of GSK2816126, an enhancer of zeste homolog 2 (EZH2) inhibitor, in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (tFL), other non-Hodgkin’s lymphomas (NHL), multiple myeloma (MM) and solid tumor.

Abstract

TPS2595Background: EZH2 is the methyltransferase component of the polycomb repressive complex 2 that represses transcription of target genes via trimethylation of histone H3 at lysine 27 (H3K27me3). These targeted genes are involved in fundamental cellular processes, e.g., development and cell differentiation. EZH2 is deregulated (via mutation or overexpression) in many cancers; increased expression correlates with more aggressive tumor progression and poor prognosis. GSK2816126, a selective and potent inhibitor of wild-type (WT) and mutant EZH2, can decrease H3K27me3 levels in vitro and has demonstrated antiproliferative activity in several cell lines derived from EZH2 WT/mutant cancers. Methods: This is a Phase I, open-label, first-time-in-human, 2-part study. Part 1 is a dose-escalation phase to determine the safety, tolerability and recommended Phase 2 dose (RP2D) of GSK2816126 in patients ( ≥ 18 years) with relapsed/refractory DLBCL, tFL, other NHL, MM and solid tumors (all with ECOG PS of 0/1). An a...