Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis
Key claim: A global Phase 1/3 trial is evaluating the efficacy and safety of selinexor combined with ruxolitinib versus placebo plus ruxolitinib in JAK inhibitor-naïve myelofibrosis patients.
Abstract
This is a global, multicenter, 2-part study to evaluate the efficacy and safety of selinexor plus ruxolitinib in JAK inhibitor (JAKi) treatment-naïve myelofibrosis (MF) participants. The study will be conducted in two phases: Phase 1 (open-label) and Phase 3 (double-blind). Phase 1 (enrollment completed) was an open-label evaluation of the safety and recommended Phase 2 dose (RP2D) of selinexor in combination with ruxolitinib and included a dose escalation using a standard 3+3 design (Phase 1a) and a dose expansion part (Phase 1b). Phase 3 (ongoing), double-blind, placebo-controlled part of the study comparing the efficacy and safety of combination therapy of selinexor + ruxolitinib with combination of placebo + ruxolitinib.
Why this matters
Selinexor + ruxolitinib is now advancing toward a confirmatory readout in JAK inhibitor-naïve myelofibrosis, positioning XPO1 inhibition as one of the leading upfront ruxolitinib-combination strategies alongside pelabresib, navitoclax, and tasquinimod for PMF/post-PV MF/post-ET MF. For the PMF natural history page, this reinforces a therapeutic landscape shift away from ruxolitinib monotherapy as the default first-line standard, with potential implications for SVR, symptom response, and VAF-reduction expectations in newly diagnosed disease.