Selinexor plus ruxolitinib in JAK inhibitor treatment-naïve myelofibrosis: SENTRY Phase 3 study design.

Selinexor is an investigational, selective oral XPO1 inhibitor that may inhibit myelofibrosis (MF)-relevant JAK/STAT and non-JAK/STAT pathways with potential synergy with ruxolitinib. SENTRY (XPORT-MF-034; NCT04562389) is a Phase 1/3 study evaluating safety and efficacy of selinexor plus ruxolitinib for treatment of patients with JAK inhibitor (JAKi) treatment-naïve MF. The Phase 1 open label portion of the study included a 3 + 3 dose escalation and dose expansion, with no dose limiting toxicities observed. Described here is the Phase 3 randomized, double-blind, placebo-controlled study designed to evaluate selinexor+ruxolitinib versus placebo+ruxolitinib in patients with JAKi treatment-naïve MF. Approximately 350 patients will be enrolled. Primary endpoints will evaluate spleen volume reduction ≥ 35% and absolute mean change in total symptom score from baseline to week 24.Clinical Trial Registration: NCT04562389 (ClinicalTrials.Gov).