Karyopharm Reports Phase 3 XPORT-EC-042 Topline Miss; sNDA Planned

What Happened
Karyopharm Therapeutics (KPTI) announced on July 30, 2026 that the Phase 3 XPORT-EC-042 trial of selinexor as maintenance therapy in TP53 wild‑type advanced or recurrent endometrial cancer did not meet its primary endpoint of progression‑free survival (PFS). In the modified intent‑to‑treat (mITT) population (n=236), median PFS was 12.75 months with once‑weekly 60 mg oral selinexor versus 7.43 months with placebo (hazard ratio 0.76; 95% CI 0.51–1.12; one‑sided p=0.0791). The company said selinexor’s safety profile was consistent with prior experience and no new safety signals were observed. Karyopharm will complete full data evaluation and plans to present results at a future medical meeting; ongoing selinexor trials are not affected.

Key Details

• Trial topline announcement date: July 30, 2026. Dose: 60 mg selinexor once weekly.
• mITT PFS: 12.75 months (selinexor) vs. 7.43 months (placebo); HR=0.76, 95% CI 0.51–1.12; one‑sided p=0.0791.
• Myelofibrosis: Karyopharm plans to submit an sNDA in August 2026 for selinexor + ruxolitinib after FDA feedback that SVR35 (≥35% spleen volume reduction) may be an accelerated‑approval surrogate; SENTRY Phase 3 shows statistically significant SVR35 at week 24 and a promising overall‑survival signal (OS is a pre‑specified secondary endpoint; trial blinded, no crossover).
• Corporate/financing: Company is exploring financing transactions and strategic alternatives with advisors (including Centerview Partners) to extend cash runway; no assurance any transaction will occur.

Why It Matters
For investors, the XPORT‑EC‑042 topline miss is material because the trial failed to meet its primary PFS endpoint despite a trend favoring selinexor in the mITT group. That may affect near‑term clinical value expectations for selinexor in endometrial cancer. Separately, the planned August 2026 sNDA for selinexor + ruxolitinib in myelofibrosis — supported by SVR35 and SENTRY data — represents a potential regulatory and commercial pathway that could be value‑creating if the FDA agrees and ultimately grants approval. The company is also actively seeking financing/strategic options to extend its cash runway; there is no guarantee those efforts will succeed.