Discovery Of Candidate Predictors Of Response To Tazemetostat In Diffuse Large B-Cell Lymphoma And Follicular Lymphoma Using Ngs Technology On Ctdna Samples Collected Pre-Treatment

Introduction: B-cell malignancies may depend on the histone methyl transferase EZH2 to perpetuate a less differentiated state, with activating mutations of EZH2 being potential oncogenic drivers. Tazemetostat, a potent, selective EZH2 inhibitor, is in Phase 2 clinical development in relapsed or refractory (RR) Non-Hodgkin Lymphoma (NHL). Objective responses were observed in patients with EZH2 mutant or wild type (WT) tumors in the Phase 1 part of the Phase 1/2 study. The ongoing Phase 2 study enrolls patients with mutant or WT EZH2 havingRR Diffuse Large B-Cell Lymphoma (DLBCL) or Follicular Lymphoma (FL) to determine efficacy and safety. The primary endpoint is overall response rate. Here we report results of a molecular analysis of circulating tumor DNA (ctDNA) collected from patient's plasma and associations with preliminary response data, including the discovery of novel candidate molecular predictors of tazemetostat response.