{"id":987593,"date":"2026-07-30T17:44:48","date_gmt":"2026-07-30T21:44:48","guid":{"rendered":"https:\/\/www.marketnewsdesk.com\/index.php\/karyopharm-announces-topline-results-from-phase-3-xport-ec-042-trial-in-endometrial-cancer\/"},"modified":"2026-07-30T17:44:48","modified_gmt":"2026-07-30T21:44:48","slug":"karyopharm-announces-topline-results-from-phase-3-xport-ec-042-trial-in-endometrial-cancer","status":"publish","type":"post","link":"https:\/\/www.marketnewsdesk.com\/index.php\/karyopharm-announces-topline-results-from-phase-3-xport-ec-042-trial-in-endometrial-cancer\/","title":{"rendered":"Karyopharm Announces Topline Results from Phase 3 XPORT-EC-042 Trial in Endometrial Cancer"},"content":{"rendered":"
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PR Newswire<\/p>\n<\/p><\/div>\n

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\n \u2013 The Trial Did Not Meet the Primary Endpoint of Progression-Free Survival (PFS) \u2013<\/i>\n <\/p>\n

\n \u2013 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 \u2013<\/i>\n <\/p>\n

\n \u2013 The Safety and Tolerability Profile was Consistent with the Known Profile of Selinexor; No New Safety Signals Were Observed \u2013<\/i>\n <\/p>\n

\n \u2013 Company Prioritizing its Resources on its Myelofibrosis and Multiple Myeloma Programs; Company to Reduce Planned Investment in Endometrial Cancer \u2013<\/i>\n <\/p>\n

\n NEWTON, Mass.<\/span>, July 30, 2026<\/span> \/PRNewswire\/ — Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced topline results from its Phase 3 XPORT-EC-042 trial evaluating selinexor as a maintenance-only therapy compared to placebo in adult patients with\u00a0TP53<\/i>\u00a0wild-type advanced or recurrent endometrial cancer. The trial did not meet its primary endpoint of progression free survival. A trend favoring the selinexor arm was observed in the modified intent to treat (mITT) population (n=236), with a median PFS of 12.75 months in the selinexor arm compared to 7.43 months in the placebo arm (hazard ratio=0.76 [95% CI: 0.51, 1.12]; one-sided p-value=0.0791). The safety and tolerability profile of selinexor was consistent with its established safety profile, with no new safety signals observed. Karyopharm intends to complete a full evaluation of the data from the XPORT-EC-042 trial and plans to present the data at a future medical meeting. The results of the XPORT-EC-042 trial do not affect ongoing trials of selinexor in other potential indications.<\/p>\n

“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 Belgium, European Network for Gynaecological Oncological Trial groups\u00a0(ENGOT) and global lead principal investigator. “The\u00a0trend for a longer progression-free survival observed in the mITT population of the selinexor arm continues to highlight the potential of XPO1 inhibition in patients with TP53<\/i>\u00a0wild-type\/pMMR endometrial cancer.”<\/p>\n

“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 the United States. “Although I am disappointed that the PFS improvement was not statistically significant, I look forward to continuing to follow these results over time and presenting the data from this important trial at an upcoming medical meeting. This patient population who have TP53<\/i>\u00a0wild-type\/pMMR advanced or recurrent endometrial cancer remains in need of new treatment options.”<\/p>\n

“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.”<\/p>\n

“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.”<\/p>\n

\n About the Phase 3 XPORT-EC-042 Trial<\/b>\n <\/p>\n

EC-042 (XPORT-EC-042; ENGOT-EN20; GOG-3083; NCT05611931<\/a>) 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<\/i>\u00a0wild-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 <\/i>wild-type tumors with proficient mismatch repair status (pMMR); or, b) TP53<\/i>\u00a0wild-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<\/i>\u00a0wild-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\u00a0a global collaboration with Foundation Medicine, Inc. to develop FoundationOne\u00aeCDx, a tissue-based comprehensive genomic profiling test to identify and enroll patients whose tumors are TP53 <\/i>wild-type. The trial is being conducted in collaboration with the European Network of Gynaecological Oncological Trial groups (ENGOT) and the GOG Foundation, Inc. \u00a0<\/p>\n

\n About Endometrial Cancer<\/b>\n <\/p>\n

Endometrial cancer (EC) is the most common gynecologic malignancy in the U.S.1<\/sup>\u00a0In 2026, approximately 68,000 uterine cancers (predominantly endometrial) are expected to be diagnosed, with approximately 14,000 deaths.1<\/sup>\u00a0 Worldwide there were about 420,368 cases with 97,723 deaths in 2022.2<\/sup>\u00a0Both incidence and mortality have continued to rise.3,4 <\/sup>\u00a0Key risk factors include obesity, type 2 diabetes, high-fat diets, tamoxifen or oral estrogen use, and delayed menopause.5<\/sup> TP53<\/i>\u00a0is a well-recognized prognostic marker for EC; >50% of advanced or recurrent EC tumors are TP53wt <\/i>(gene for tumor protein P53; wild-type), and ~40%-55% are both TP53wt<\/i>\u00a0and mismatch repair-proficient (pMMR).6-8 <\/sup>While immune checkpoint inhibitors have shown benefit in patients with mismatch repair\u2013deficient (dMMR) and pMMR, the magnitude of benefit is greater for patients with dMMR tumors versus pMMR tumors.9-10 <\/sup>\u00a0There remains an unmet need for targeted therapies for patients with pMMR EC.11 <\/sup><\/p>\n

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\n 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<\/a>.\u00a0 Accessed February 8, 2026 <\/span>\n <\/p>\n<\/td>\n<\/tr>\n

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\n 2. IARC GLOBOCAN 2022, Global Estimates <\/span>\n <\/p>\n<\/td>\n<\/tr>\n

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\n 3. Lu KH, et al. N Engl J Med. 2020;383:2053-2064\u00a0 <\/span>\n <\/p>\n<\/td>\n<\/tr>\n

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\n 4. NCI. Cancer stat facts: uterine cancer. https:\/\/seer.cancer.gov\/statfacts\/html\/corp.html<\/a>.\u00a0 Accessed October 7, 2025\u00a0 <\/span>\n <\/p>\n<\/td>\n<\/tr>\n

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\n 5. American Cancer Society, Endometrial Cancer Risk Factors, 2025 <\/span>\n <\/p>\n<\/td>\n<\/tr>\n

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\n 6. Leslie KK, et al. Gynecol Oncol. 2021;161(1):113-121.\u00a0 <\/span>\n <\/p>\n<\/td>\n<\/tr>\n

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\n 7. Vergote I, et al. J Clin Oncol. 2023;41(35):5400-5410.\u00a0 <\/span>\n <\/p>\n<\/td>\n<\/tr>\n

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\n 8. Mirza MR, et al. Presentation at: ESMO Congress; October 20-24, 2023 <\/span>\n <\/p>\n<\/td>\n<\/tr>\n

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\n 9. Mirza MR, et al. N\u00a0Engl\u00a0J Med. 2023; 388:2145-2158. <\/span>\n <\/p>\n<\/td>\n<\/tr>\n

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\n 10. Eskander RN, et al. N Engl J Med. 2023;388:2159-2170.\u00a0 <\/span>\n <\/p>\n<\/td>\n<\/tr>\n

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\n 11. Makker V, et al. Gynecol Oncol.\u00a02024 Jun:185: 202-211 <\/span>\n <\/p>\n<\/td>\n<\/tr>\n<\/table><\/div>\n

\n About XPOVIO\u00ae (selinexor)<\/b>\n <\/p>\n

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 U.S. in multiple oncology indications, including: (i) in combination with VELCADE\u00ae (bortezomib) and dexamethasone (XVd) in adult patients with multiple myeloma after at least one prior therapy; and (ii) in combination with dexamethasone in adult patients with heavily pre-treated multiple myeloma. XPOVIO\u00ae (also known as NEXPOVIO\u00ae in certain countries) has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, Mainland China, Taiwan, Hong Kong, Australia, South Korea, Singapore, Israel, and Canada. XPOVIO\u00ae\/NEXPOVIO\u00ae is marketed in these respective ex-U.S. territories by Karyopharm’s partners: Antengene, Menarini, Neopharm, and FORUS. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high-unmet need cancer indications.<\/p>\n

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<\/a><\/p>\n

XPOVIO\u00ae (selinexor) is a prescription medicine approved:<\/p>\n