Therapeutic RSK1 Targeting in Myelofibrosis
Key claim: A phase Ib dose-escalation study is evaluating PMD-026, an oral RSK1 inhibitor, as a novel therapeutic approach in myelofibrosis patients.
Abstract
This is a phase Ib study evaluating PMD-026, an oral inhibitor of ribosomal protein S6 kinase A1 (RSK1), in participants with myelofibrosis (MF).The dose escalation portion utilizes a standard 3+3 design to evaluate two dose levels with an additional dose de-escalation portion to identify the recommended phase II dose (RP2D); subsequently, an additional 6 patients will be enrolled in the dose expansion portion evaluating the efficacy of PMD-026.
Why this matters
PMD-026 introduces RSK1 inhibition as a mechanistically novel target in myelofibrosis, joining a growing roster of non-JAK pathway approaches (BET, LSD1, XPO1, PI3K-δ, IL-1β, S100A9) being tested in PMF. For a subtype where ruxolitinib resistance and disease modification remain central unmet needs, first-in-class mechanisms entering phase Ib expand the pipeline of options that could eventually be combined with or sequenced after JAK inhibition.