Karyopharm Stock Plummets Over 60% After Endometrial Cancer Drug Fails Late-Stage Trial

Karyopharm Therapeutics (NASDAQ: KPTI) shares plummeted more than 67% in morning trading after the company announced its late-stage clinical trial for selinexor in patients with endometrial cancer failed to meet its primary endpoint.

Trial Fails to Meet Primary Goal

The Phase 3 XPORT-EC-042 study evaluated selinexor as a maintenance therapy for patients with a specific type of advanced or recurrent endometrial cancer. According to the company, the trial did not demonstrate a statistically significant improvement in progression-free survival compared to a placebo.

While Karyopharm noted a numerical trend favoring the selinexor arm by over five months, the lack of statistical significance constitutes a trial failure. In response, the company stated it will scale back planned investments in its endometrial cancer program to reallocate resources toward its myelofibrosis and multiple myeloma franchises.

Analyst Downgrades and Market Impact

The market reaction was swift and severe, with the stock hitting a new 52-week low of $2.09 intraday. The clinical setback prompted immediate downgrades from Wall Street analysts, who cited the loss of a major potential growth catalyst.

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Key analyst actions included:

• Baird: Downgraded the stock to Neutral from Outperform and slashed its price target from $15.00 to $3.00.
• H.C. Wainwright: Moved its rating to Neutral from Buy and cut its price target from $13.00 to $3.00.

Pipeline Focus Shifts

Despite the trial failure, Karyopharm confirmed it still plans to submit a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) in August 2026. The application is for selinexor in combination with ruxolitinib for treating myelofibrosis and will include a request for Priority Review under an accelerated approval pathway.

However, this positive development in a separate program was heavily overshadowed by the high-profile failure in endometrial cancer, which investors had viewed as a key component of the company's near-term valuation.