Karyopharm Announces Topline Results from Phase 3 XPORT-EC-042 Trial in Endometrial Cancer
Rhea-AI Summary
Karyopharm Therapeutics (Nasdaq: KPTI) reported topline Phase 3 results from the global XPORT-EC-042 trial evaluating once-weekly oral selinexor as maintenance monotherapy versus placebo in 257 adults with TP53 wild-type advanced or recurrent endometrial cancer.
The trial 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 selinexor versus 7.43 months with placebo (hazard ratio 0.76; 95% CI: 0.51–1.12; one-sided p=0.0791), corresponding to a 5.3‑month difference favoring selinexor. As of data cut-off, 106 PFS events had occurred in the mITT group.
The safety and tolerability of selinexor were consistent with its established profile, and no new safety signals were observed. Karyopharm will fully analyze the dataset, continue to follow patients for longer-term outcomes, and plans to present detailed results at a future medical meeting. The company said these findings do not affect ongoing selinexor trials in other indications and that it will reduce planned investment in endometrial cancer while prioritizing its myelofibrosis and multiple myeloma programs, with several myelofibrosis milestones expected in the second half of 2026.
Positive
- Median PFS 12.75 vs 7.43 months in mITT, favoring selinexor
- Hazard ratio 0.76 (95% CI: 0.51–1.12) indicates numerically longer PFS
- No new safety signals; safety consistent with known selinexor profile
- Trial fully enrolled 257 patients in global randomized Phase 3 setting
- Company prioritizing myelofibrosis and multiple myeloma with key milestones expected in 2H 2026
Negative
- Primary PFS endpoint not met in Phase 3 XPORT-EC-042
- One-sided p-value 0.0791 indicates PFS improvement not statistically significant
- Planned investment in endometrial cancer reduced following trial results
News Market Reaction – KPTI
In the Jul 31 session, KPTI declined 72.61%, reflecting a significant negative market reaction. Argus tracked a trough of -72.7% from its starting point during tracking. Our momentum scanner triggered 66 alerts that day, indicating high trading interest and price volatility. Trading volume was exceptionally heavy at 27.9x the daily average, suggesting significant selling pressure.
Data tracked by StockTitan Argus on the day of publication.
AI-generated analysis. How Rhea-AI works. Not financial advice.
– The Trial Did Not Meet the Primary Endpoint of Progression-Free Survival (PFS) –
– A Trend Favoring the Selinexor Arm was Observed with a 5.3 Month Improvement in Median PFS Relative to the Placebo Arm in the mITT Population; Company Plans to Continue to Follow Patients for Longer-Term Outcomes –
– The Safety and Tolerability Profile was Consistent with the Known Profile of Selinexor; No New Safety Signals Were Observed –
– Company Prioritizing its Resources on its Myelofibrosis and Multiple Myeloma Programs; Company to Reduce Planned Investment in Endometrial Cancer –
"These results are meaningful for a patient population lacking effective maintenance therapies that can delay disease progression," said Professor Ignace Vergote, MD, gynecologic oncologist at the Catholic University Leuven in
"Delaying the progression of cancer by five months at the median is a meaningful and encouraging outcome," said Dr. Robert Coleman, M.D., FACOG, FACS, of Texas Oncology and the Gynecologic Oncology Group (GOG) and lead principal investigator in
"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," said Reshma Rangwala, MD, PhD, Chief Medical Officer and Head of Research at Karyopharm. "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."
"While the results we are announcing today fell short of our expectations, they do not diminish our confidence in the broader potential of selinexor and benefit of XPO1 inhibition," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "We remain focused on maximizing our opportunity in myelofibrosis and continuing to build on our profitable multiple myeloma business. Looking ahead, we expect several important milestones in our myelofibrosis program over the next year, including the submission of our sNDA, the potential addition of selinexor to relevant compendia guidelines and topline data from the 60 mg cohort of the Phase 2 SENTRY-2 trial, each anticipated in the second half of 2026."
About the Phase 3 XPORT-EC-042 Trial
EC-042 (XPORT-EC-042; ENGOT-EN20; GOG-3083; NCT05611931) is a global, Phase 3, randomized, double-blind, placebo-controlled clinical trial evaluating selinexor as a maintenance-only therapy following chemotherapy or chemotherapy plus a checkpoint inhibitor in patients with TP53 wild-type advanced or recurrent endometrial cancer (N=257). Patients were randomized 1:1 to receive either a 60 mg, once-weekly, administration of oral selinexor or placebo until disease progression. The trial includes two patient populations, for which the primary endpoint of progression free survival was tested sequentially: 1) a modified intent to treat population (mITT) that includes patients with either, a) TP53 wild-type tumors with proficient mismatch repair status (pMMR); or, b) TP53 wild-type tumors with deficient mismatch repair status (dMMR), who are medically ineligible to receive checkpoint inhibitors; and, 2) the trial's original intent to treat (ITT) population, which includes all patients enrolled in the trial whose tumors are TP53 wild-type, regardless of MMR status. Overall survival is a key secondary endpoint. The mITT population enrolled 236 patients. As of the data cut-off, 106 progression free survival events as assessed by the investigator had been observed in the mITT population. In connection with the EC-042 trial, Karyopharm entered into a global collaboration with Foundation Medicine, Inc. to develop FoundationOne®CDx, a tissue-based comprehensive genomic profiling test to identify and enroll patients whose tumors are TP53 wild-type. The trial is being conducted in collaboration with the European Network of Gynaecological Oncological Trial groups (ENGOT) and the GOG Foundation, Inc.
About Endometrial Cancer
Endometrial cancer (EC) is the most common gynecologic malignancy in the
1. American Cancer Society. Cancer Facts & Figures 2026. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2026/2026-cancer-facts-and-figures.pdf. Accessed February 8, 2026 |
2. IARC GLOBOCAN 2022, Global Estimates |
3. Lu KH, et al. N Engl J Med. 2020;383:2053-2064 |
4. NCI. Cancer stat facts: uterine cancer. https://seer.cancer.gov/statfacts/html/corp.html. Accessed October 7, 2025 |
5. American Cancer Society, Endometrial Cancer Risk Factors, 2025 |
6. Leslie KK, et al. Gynecol Oncol. 2021;161(1):113-121. |
7. Vergote I, et al. J Clin Oncol. 2023;41(35):5400-5410. |
8. Mirza MR, et al. Presentation at: ESMO Congress; October 20-24, 2023 |
9. Mirza MR, et al. N Engl J Med. 2023; 388:2145-2158. |
10. Eskander RN, et al. N Engl J Med. 2023;388:2159-2170. |
11. Makker V, et al. Gynecol Oncol. 2024 Jun:185: 202-211 |
About XPOVIO® (selinexor)
XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor compound for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved and marketed by Karyopharm in the
For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at: Tel: +1 (888) 209-9326; Email: medicalinformation@karyopharm.com
XPOVIO® (selinexor) is a prescription medicine approved:
- In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
- In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐CD38 monoclonal antibody (Xd).
SELECT IMPORTANT SAFETY INFORMATION
Warnings and Precautions
Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions
- The most common adverse reactions (≥
20% ) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10% ) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia, and neutropenia. In theBOSTON trial, fatal adverse reactions occurred in6% of patients within 30 days of last treatment. Serious adverse reactions occurred in52% of patients. Treatment discontinuation rate due to adverse reactions was19% . - The most common adverse reactions (≥
20% ) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in9% of patients. Serious adverse reactions occurred in58% of patients. Treatment discontinuation rate due to adverse reactions was27% .
Use In Specific Populations
Lactation: Advise not to breastfeed.
For additional product information, including full prescribing information, please visit www.XPOVIO.com.
To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1‐888‐209‐9326 or FDA at 1‐800‐FDA‐1088 or www.fda.gov/medwatch.
About Karyopharm Therapeutics
Karyopharm Therapeutics is a commercial-stage pharmaceutical company pioneering the science of nuclear export inhibition to develop differentiated therapies for patients with cancer. The Company's lead therapy, XPOVIO® (selinexor), is a first-in-class inhibitor of exportin 1 (XPO1). XPOVIO is marketed by the Company in the U.S. for adults with relapsed or refractory multiple myeloma and is approved as XPOVIO or NEXPOVIO® in more than 50 ex-U.S. countries and territories. Building on its leadership in XPO1 biology, Karyopharm is advancing selinexor's potential in hematological cancers, including in myelofibrosis. The Company is also exploring opportunities to evaluate XPO1 inhibition across myeloproliferative neoplasms using next-generation compounds, including eltanexor. Headquartered in Newton, Massachusetts, Karyopharm has an established, efficient, and scalable commercial infrastructure to bring novel therapeutic options to patients with cancer. For more information, visit www.karyopharm.com and follow Karyopharm on LinkedIn and on X at @Karyopharm.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the ability of selinexor and eltanexor to treat patients with multiple myeloma, endometrial cancer, myelofibrosis, and other diseases; expectations with respect to the clinical development plans, regulatory discussions and potential regulatory submissions for selinexor; and expectations regarding the timing, presentation and publication of topline data, publications or compendia listings related to selinexor. Such statements are subject to numerous important factors, risks, and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to obtain and retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical trials, including subsequent analysis of existing data and new data received from ongoing and future trials; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical trials; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to enroll patients in its clinical trials; unplanned cash requirements and expenditures; substantial doubt exists regarding Karyopharm's ability to continue as a going concern; development or regulatory approval of drug candidates by Karyopharm's competitors for products or product candidates in which Karyopharm is currently commercializing or developing; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any of its products or product candidates. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended March 31, 2026, which was filed with the Securities and Exchange Commission (SEC) on May 14, 2026, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.
XPOVIO® and NEXPOVIO® are registered trademarks of Karyopharm Therapeutics Inc.
View original content to download multimedia:https://www.prnewswire.com/news-releases/karyopharm-announces-topline-results-from-phase-3-xport-ec-042-trial-in-endometrial-cancer-302839314.html
SOURCE Karyopharm Therapeutics Inc.