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MANIFEST update: pelabresib clinical and pathological investigations

Srdan Verstovsek, MD, PhD, University of Texas MD Anderson Cancer Center, Houston, TX, shares preliminary findings from the ongoing Phase II MANIFEST study (NCT02158858) of pelabresib with and without ruxolitinib for the treatment of myelofibrosis (MF). Pelabresib is a first-in-class, selective small-molecule BET inhibitor, shown to modify the expression of genes involved in NFκB signaling in patients with MF. The multi-arm study investigated pelabresib as a single agent in patients intolerant or refractory to ruxolitinib, or as an add on in patients receiving ruxolitinib with a suboptimal response. Updated data showed that, in both trial arms, pelabresib reduced bone marrow fibrosis, decreased megakaryocyte density and increased erythroid progenitor numbers. Additionally, treatment was able to reduce spleen volume and improve symptoms. Dr Verstovsek outlines the plans for a Phase III trial of pelabrasib. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.