A phase 2 study to assess the safety and efficacy of bomedemstat (IMG-7289) in combination with momelotinib in patients with myelofibrosis.

Abstract

TPS6605 Background: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by splenomegaly, cytopenias, inflammatory symptoms, and progressive marrow fibrosis. Momelotinib, a JAK1/JAK2 and ACVR1 inhibitor, improves splenomegaly and anemia; however, a substantial proportion of patients experience inadequate spleen, symptom, or hematologic responses. Bomedemstat (IMG-7289), an oral irreversible inhibitor of lysine-specific demethylase 1 (LSD1), has demonstrated disease-modifying activity in MF, including effects on megakaryopoiesis, inflammatory signaling, and fibrosis. Preclinical and clinical data support complementary mechanisms between JAK inhibition and LSD1 inhibition. Methods: This is an open-label, single-arm, multicenter phase 2 study enrolling approximately 50–60 adults with primary or secondary MF (post–polycythemia vera or post–essential thrombocythemia) with intermediate-2 or high-risk disease. All patients receive momelotinib 200 mg orally once daily. After 12 weeks of momelotinib monotherapy, patients with protocol-defined suboptimal response—based on spleen volume reduction, symptom improvement, hematologic parameters, or transfusion requirements—initiate combination therapy with bomedemstat 50 mg orally once daily, with dose titration per MF-specific guidelines, through week 24. Two cohorts are included: (1) patients previously treated with momelotinib who demonstrate suboptimal response after ≥12 weeks of therapy, and (2) patients with baseline cytopenias initiating momelotinib within the study who demonstrate suboptimal response at week 12. The primary endpoint is the proportion of patients achieving ≥35% spleen volume reduction at week 24 by MRI or CT. Secondary endpoints include ≥50% reduction in total symptom score, changes in symptom burden, transfusion independence, hematologic responses, overall response rate, duration of response, progression-free survival, overall survival, and safety and tolerability. Exploratory endpoints include molecular and biomarker analyses assessing changes in driver mutation allele burden, inflammatory cytokines, and markers of differentiation and fibrosis. The study will run in 5 Countries (UK, France, Spain, Dubai, USA), for a total of 20 Sites. Enrollment expected to start in September 2026. Clinical trial information: ISRCTN98283910.