Karyopharm reported mixed top-line results from its Phase 3 Sentry trial of 60-mg Xpovio (selinexor) plus ruxolitinib in front-line myelofibrosis. The study met the first co-primary endpoint, demonstrating statistically significant improvement in spleen volume reduction of at least 35%, with rapid, deep, and sustained knockdown. Karyopharm said symptom changes were comparable across arms, while the second endpoint did not reach statistical significance. Still, the company pointed to an overall survival signal and plans a meeting with the U.S. FDA about the feasibility of an sNDA filing based on the dataset. The readout adds pressure to competitor trial designs and outcomes in myelofibrosis, where endpoints that combine spleen and patient-reported outcomes heavily influence regulatory review. Karyopharm’s next steps will focus on how the agency weighs the single endpoint success against the missed endpoint and what statistical framing the label strategy could require. For investors, the announcement shifts the decision tree from “clinical efficacy only” to “regulatory interpretation,” with a potential filing path contingent on FDA guidance after the scheduled discussion.