Phase 2 Study to Assess the Safety and Efficacy of Bomedemstat (MK3543) in Combination with Ruxolitinib in Patients with Myelofibrosis
Abstract
Background
Approximately 50% of patients with myelofibrosis (MF) discontinue ruxolitinib after 3 years, mostly due to disease progression, suboptimal response or cytopenia. Outcome after ruxolitinib discontinuation is poor with a median overall survival (OS) of approximately 14 months. Lysine-specific demethylase-1 (LSD1) is a histone demethylase critical for self-renewal of malignant hematopoietic stem cells and for maturation of progenitor cells. Bomedemstat is an oral LSD1 inhibitor clinically active in patients with myeloproliferative neoplasms (MPN) and has shown clinical activity as a single-agent in patients with MF.
Aims
This is an ongoing, open-label, Phase 2 study of the combination of bomedemstat and ruxolitinib in treatment-naïve patients with MF or those with a sub-optimal response to ruxolitinib. The objectives of this are to evaluate the safety and tolerability of the combination, the optimal dosing of bomedemstat in this regimen, and to assess the efficacy of the combination as assessed by spleen size reduction and symptom reduction using the Myelofibrosis Symptom Assessment Form (MFSAF).
Methods
Cohort A is comprised of patients with a sub-optimal response to an adequate trial of ruxolitinib defined as splenomegaly not reduced by >35% from baseline or symptoms scores that have not improved by >50%. Cohort A patients must have been on a stable dose of ruxolitinib for ≥8wks. Cohort B is comprised of treatment-naïve patients with MF who require treatment per…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 24 participants or records.
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