Newton, Massachusetts-based Karyopharm Therapeutics (Nasdaq: KPTI) reported that selinexor (Xpovio) combined with ruxolitinib nearly doubled the spleen volume response rate versus ruxolitinib alone in JAK inhibitor-naïve myelofibrosis, with Phase III data simultaneously published in the Journal of Clinical Oncology at ASCO 2026. The trial achieved onme of its co-primary endpoints in relation to spleen volume reduction, but fell short in the second co-primary endpoint average change in total symptom score.
The SENTRY trial (NCT04562389) is a randomized, placebo-controlled Phase III study enrolling 353 JAKi-naïve myelofibrosis patients with platelet counts above 100 × 10⁹/L, randomized 2:1 to selinexor 60 mg once weekly plus ruxolitinib or placebo plus ruxolitinib. On the co-primary endpoint of spleen volume reduction ≥ 35% (SVR35) at week 24, 49.8% of patients in the combination arm responded versus 28.0% in the control arm (odds ratio 2.58; 95% CI 1.60–4.17; p < 0.05).
The second co-primary endpoint — average change in absolute total symptom score over 24 weeks — did not reach statistical significance; the adjusted mean difference was 0.97 points (95% CI −1.07 to 3.02; p=0.825), with similar symptom improvement observed across both arms. A pre-specified secondary analysis of overall survival showed a hazard ratio of 0.43 (95% CI 0.19–1.00; nominal one-sided p=0.022), with Kaplan-Meier curve separation emerging around month 9 and 95.3% of combination-arm patients alive at the February 2026 data cut versus 89.8% in the control arm. Grade 3+ treatment-emergent adverse events occurred in 70% of the combination arm versus 50% of controls, driven primarily by hematologic toxicity; thrombocytopenia (59% vs 43%) and nausea (57% vs 17%) were the most differentiated all-grade events.
Selinexor inhibits exportin 1 (XPO1), a nuclear export protein, retaining tumor suppressor proteins in the nucleus — a mechanism distinct from JAK inhibition and theoretically complementary to ruxolitinib's pathway. The myelofibrosis combination landscape also includes Syndax's axatilimab and Bristol Myers Squibb's Reblozyl (luspatercept) in related settings, though cross-trial comparisons are limited by differing populations and endpoints.