MPN-377: Updated Results from a Phase 1/2 Clinical Trial of Tagraxofusp, a CD123-Targeted Therapy, in Patients with Poor-Risk Myelofibrosis

Abstract

Background: Most patients (pts) with intermediate- and high-risk myelofibrosis (MF) achieve spleen volume reduction and symptomatic improvement but no significant impact on the driver mutations or risk to transformation. Furthermore, patients with baseline thrombocytopenia, monocytosis, or high-risk genetic features and those in accelerated phase fare poorly. There is a need for drug development in MF to focus on identifying new therapeutic targets. A novel approach involves tagraxofusp (TAG), a CD123-targeted therapy, approved for blastic plasmacytoid dendritic cell neoplasm in 2018 and noted to have preclinical activity in MF. Herein, we present updated results from a phase I/II study on TAG monotherapy in patients with relapsed/refractory (R/R) MF. Aims: To assess safety and evaluate efficacy of TAG in patients with relapsed, refractory MF using IWG-MRT response criteria. Methods: Multicenter ongoing trial with TAG administered as a daily IV infusion at 7, 9, or 12 mcg/kg on days 1–3 every 21 days (cycle 1–4), 28 days (cycles 5–7), and 42 days (cycles 8+) in stage 1 and 12 mcg/kg in the ongoing stage 2. Results: Thirty-two pts with a median age of 69.5 yrs have been treated: 25% had baseline monocytosis and thrombocytopenia, including 31% with platelets 50% spleen reduction; 11 of 24 (46%) had symptom burden reduction, including three pts with stringent IWG-MRT criteria; the median overall survival was 31 mos. Conclusions: The interim results demonstrate clinical efficacy and safety of TAG monotherapy in a cohort of poor-risk MF patients, including some with associated monocytosis. ( NCT02268253 )