Phase 1/2 Study of the Activin Receptor-like Kinase-2 Inhibitor Zilurgisertib (INCB000928, LIMBER-104) As Monotherapy or with Ruxolitinib in Patients with Anemia Due to Myelofibrosis

Introduction:Elevated levels of the iron regulator hepcidin can cause functional iron deficiency anemia. Hepcidin dysregulation is central to anemia of chronic inflammation observed in several malignancies including myelofibrosis (MF). Activin receptor-like kinase-2 (ALK2 [ie, ACVR1]) contributes to MF-associated anemia via hepcidin upregulation. We evaluated the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of zilurgisertib-a potent and selective oral ALK2 inhibitor-in patients (pts) with anemia due to MF.