On July 30, 2026 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported topline results from its Phase 3 XPORT-EC-042 trial evaluating selinexor as a maintenance-only therapy compared to placebo in adult patients with TP53 wild-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.
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"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 (ENGOT) and global lead principal investigator. "The trend 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 wild-type/pMMR endometrial cancer."
"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 wild-type/pMMR advanced or recurrent endometrial cancer remains in need of new treatment options."
"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 FoundationOneCDx, 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 U.S.1 In 2026, approximately 68,000 uterine cancers (predominantly endometrial) are expected to be diagnosed, with approximately 14,000 deaths.1 Worldwide there were about 420,368 cases with 97,723 deaths in 2022.2 Both incidence and mortality have continued to rise.3,4 Key risk factors include obesity, type 2 diabetes, high-fat diets, tamoxifen or oral estrogen use, and delayed menopause.5 TP53 is a well-recognized prognostic marker for EC; >50% of advanced or recurrent EC tumors are TP53wt (gene for tumor protein P53; wild-type), and ~40%-55% are both TP53wt and mismatch repair-proficient (pMMR).6-8 While immune checkpoint inhibitors have shown benefit in patients with mismatch repair–deficient (dMMR) and pMMR, the magnitude of benefit is greater for patients with dMMR tumors versus pMMR tumors.9-10 There remains an unmet need for targeted therapies for patients with pMMR EC.11
1. American Cancer Society. Cancer Facts & Figures 2026. View Source 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. View Source 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 (Free ESMO Whitepaper) 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 U.S. in multiple oncology indications, including: (i) in combination with VELCADE (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 (also known as NEXPOVIO 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/NEXPOVIO 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.
For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at: Tel: +1 (888) 209-9326; Email: [email protected]
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 the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
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 in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
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.
(Press release, Karyopharm, JUL 30, 2026, View Source [SID1234669535])