Karyopharm Therapeutics reported topline results from its Phase 3 SENTRY trial of selinexor in combination with ruxolitinib in frontline myelofibrosis, stating that the study met its first co-primary endpoint but not its second. The randomized, double-blind, placebo-controlled trial enrolled 353 patients and compared once-weekly selinexor 60 mg plus ruxolitinib with placebo plus ruxolitinib. According to the company, the combination demonstrated a statistically significant improvement in the proportion of patients achieving at least a 35% reduction in spleen volume (SVR35) at week 24, while symptom improvement, measured by absolute total symptom score (Abs-TSS), was similar in both arms and did not reach statistical significance between groups.
Karyopharm reported that 50% of patients receiving selinexor plus ruxolitinib achieved SVR35 at week 24, compared with 28% of patients on ruxolitinib alone (one-sided p<0.0001). The company said spleen responses occurred rapidly in the combination arm, with 49% of patients reaching SVR35 by week 12 versus 20% in the ruxolitinib-alone arm, and were sustained through week 36, when 47% of patients on the combination and 23% on ruxolitinib alone met SVR35. For symptoms, the mean change in Abs-TSS at week 24 from baseline was a 9.89‑point improvement in the combination arm and a 10.86‑point improvement in the ruxolitinib-alone arm, which the company described as comparable across the two treatment groups.
The topline analysis also showed what Karyopharm characterized as a promising overall survival signal favoring the selinexor combination. The reported hazard ratio for overall survival was 0.43 (95% confidence interval 0.19–1.00; nominal one-sided p=0.0222) for selinexor plus ruxolitinib versus ruxolitinib alone, and the company said it intends to continue following patients until overall survival data mature. Post-hoc landmark analyses at weeks 12 and 24 suggested that achieving SVR35 may be associated with overall survival outcomes.
An exploratory analysis of variant allele frequency (VAF) reductions for JAK2, MPL and CALR showed that 32% of patients in the combination arm achieved at least a 20% reduction at week 24 compared with 24% in the ruxolitinib-alone arm, which the company described as evidence of potential disease modification. Across other secondary and exploratory endpoints, including progression-free survival, hemoglobin stabilization and bone marrow fibrosis improvement, Karyopharm said no meaningful differences were observed between the two arms at the February 20, 2026 data cutoff, and it plans further evaluation as these endpoints mature.
Patients in SENTRY were randomized in a 2:1 ratio to receive selinexor plus ruxolitinib or placebo plus ruxolitinib, with the ruxolitinib dose determined by baseline platelet count according to prescribing information. Karyopharm reported that no new safety signals were identified in the trial. The company said it plans to meet with the U.S. Food and Drug Administration to discuss the totality of the SENTRY data and a potential supplemental new drug application filing, and noted that it will also share the results with regulators, clinicians and patient advocacy groups.
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