Phase 2 study of the lysine-specific demethylase 1 (LSD1) inhibitor bomedemstat in patients with polycythemia vera (PV)
Abstract
TPS6595 Background: PV is a myeloproliferative neoplasm (MPN) characterized by clonal erythrocytosis that is driven by mutations in JAK2. Currently available treatments reduce thrombotic risk and symptom burden but have little impact on disease course or risk of progression to post-PV myelofibrosis (PPV-MF) or acute myeloid leukemia (AML). There remains a need for novel treatments that can alter the natural history of PV. LSD1 is an enzyme that regulates megakaryocytes and erythrocyte maturation. Bomedemstat is an irreversible inhibitor of LSD1 that has been shown to have manageable safety and clinically relevant activity in other JAK2-mutation–prevalent MPNs (essential thrombocythemia and myelofibrosis). Here, we describe the methods for an open-label phase 2 study (NCT05558696) that has been designed to evaluate the efficacy and safety of bomedemstat in patients with PV who are resistant to or intolerant of standard cytoreductive therapy. Methods: Eligible patients are ≥18 years, have a confirmed diagnosis of PV per World Health Organization 2016 diagnostic criteria, a bone marrow fibrosis score of grade 0 or 1, an ECOG performance status of 0-2, a platelet count of ≥250 × 109/L, an absolute neutrophil count of ≥1.5 × 109/L, and resistance to or intolerance of ≥1 standard cytoreductive therapy. All patients will receive bomedemstat at a starting dose of 40 mg/d by mouth for 36 weeks, with dose titration to a hematocrit target of <45% with no grade ≥1 thrombocytopenia.…
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