A Phase 1 Study Of Incb057643 Monotherapy In Patients With Relapsed Or Refractory Myelofibrosis (Incb 57643-103).

Background: Activation of transcription factors that regulate oncogenic processes is frequently observed in cancers such as myelofibrosis (MF). In preclinical studies, tumors associated with dysregulation of transcription factors appear to be responsive to inhibition of bromodomain and extra-terminal motif (BET) protein [Delmore JE, et al. Cell 2011; Shimamura T, et al. Clin Cancer Res 2013]. In addition to exerting a direct effect on tumor cells, BET inhibitors may also modulate tumorigenic inflammation; in a mouse model of MF, BET inhibition in combination with the Janus kinase inhibitor ruxolitinib resulted in decreased inflammation and reduced disease burden [Kleppe M, et al. Cancer Cell 2018]. In the first-in-human study INCB 57643-101, the small-molecule BET inhibitor INCB057643, was safe and generally well tolerated as monotherapy, and demonstrated preliminary efficacy in 2 out of 3 patients with MF when administered alone or in combination with ruxolitinib [Falchook G, et al. Clin Cancer Res 2020]. The INCB 57643-103 trial is designed to further evaluate the safety and tolerability of INCB057643 monotherapy in patients with relapsed or refractory MF.