Phase III SIENDO/ENGOT-EN5/GOG-3055 study of Xpovio meets primary endpoint in endometrial cancer.

The SIENDO study met its primary endpoint of a statistically significant improvement in median progression-free survival (PFS) compared to placebo. Selinexor-treated patients had a median PFS of 5.7 months compared to 3.8 months for patients on placebo, representing an improvement of 50%, with a hazard ratio (HR) of 0.70 (p=0.0486), representing a 30% reduction in the risk of disease progression or death. Selinexor demonstrated a sustained and long-term improvement as seen at 12 months with a 37% increase in probability that selinexor-treated patients will be in remission compared to patients on no treatment, or today's standard of "watch and wait." In this study, selinexor was well tolerated with no new safety signals identified, and a low discontinuation rate of 10.5% due to adverse events.

Karyopharm will work with investigators and the FDA to complete a full evaluation of the SIENDO data. The preliminary data identified a pre-specified subgroup (wild-type p53, known as "the guardian of the genome") which achieved a statistically significant reduction in the risk of disease progression or death (current n=103): HR 0.38; p=0.0006. In this pre-specified subgroup, selinexor-treated patients had a median PFS of 13.7 months compared to 3.7 months for patients on placebo with a HR of 0.38 (p=0.0006), representing a 62% reduction in the risk of disease progression or death. Inhibition of XPO1 by selinexor leads to the nuclear accumulation of p53, a well-established tumor suppressor protein, which Karyopharm believes allows p53 to carry out its tumor suppressor function. The Company plans to submit a supplemental New Drug Application (sNDA) to the FDA during the first half of 2022. The Company also plans to submit the detailed results from the study for presentation at upcoming medical meetings in the first half of 2022.