Karyopharm Therapeutics’ Phase III XPORT-EC-042 clinical trial assessing selinexor has failed to meet its primary endpoint of progression-free survival (PFS) in patients with advanced or recurrent endometrial cancer with TP53 wild-type tumours.
Following the results, the company’s shares dropped sharply in after-hours trading. The stock, which closed the regular session up 2.19% at $7.01, fell by 68.47% to $2.21 after the announcement.
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The global, randomised, double-blind, placebo-controlled trial enrolled 257 adults.
Participants received either a 60mg weekly dose of oral selinexor or a placebo after completing chemotherapy or chemotherapy combined with a checkpoint inhibitor.
PFS was the main outcome, which was assessed in two groups of patients, evaluated one after the other.
The modified intent-to-treat (mITT) population, which included 236 patients with either TP53 wild-type proficient mismatch repair (pMMR) tumours or, ineligible for checkpoint inhibitors, those with deficient mismatch repair (dMMR) tumours, was a primary focus of analysis.
Results indicated a median progression-free survival of 12.75 months in the selinexor arm, compared to 7.43 months for placebo in the mITT group, with a hazard ratio of 0.76.
Despite this observed trend, statistical significance was not reached for the primary endpoint. Safety and tolerability findings were aligned with selinexor’s established profile, with no new safety issues reported.
Karyopharm chief medical officer and research head Dr Reshma Rangwala said: “While disappointed by these unexpected results, we believe they advance the scientific understanding of XPO1 inhibition for tens of thousands of endometrial cancer patients worldwide.
“We are deeply committed to further investigating these data. I would like to thank all of the patients, their families and the clinical trial investigators and their staff, as well as ENGOT and GOG, for participating in this trial.”
Karyopharm intends to continue long-term follow-up for survival outcomes and will present comprehensive data at a future medical meeting.
The company plans to prioritise its resources towards myelofibrosis and multiple myeloma programmes, with reduced investment in endometrial cancer studies.
The outcome of this trial does not impact ongoing investigations of selinexor in other indications.
In September 2025, Karyopharm reached a significant milestone by completing patient enrolment for its Phase III SENTRY trial.
