Karyopharm Therapeutics Inc. recently reported topline results from its Phase 3 SENTRY trial, a randomized, double-blind, placebo-controlled trial of 60 mg selinexor in combination with ruxolitinib in frontline myelofibrosis (n=353). The trial met the first co-primary endpoint, demonstrating statistically significant improvement in spleen volume reduction of 35% or more (SVR35) for patients treated with the combination of selinexor plus ruxolitinib, with rapid, deep and sustained spleen volume reduction rates seen in the combination arm. The mean change in absolute total symptom score (Abs-TSS) at week 24 relative to baseline was comparable across the two arms with similar symptom improvement relative to baseline; the difference across the two arms was not statistically significant. Importantly, the topline results suggest a promising signal in overall survival (OS) for the combination arm.

Spleen Volume: 50% of patients who received the combination of selinexor plus ruxolitinib achieved a statistically significant improvement in SVR35 at week 24 compared to 28% of patients who received ruxolitinib alone (one-sided p<0.0001). Patients on the combination achieved rapid spleen reduction with 49% already achieving SVR35 at week 12 compared to 20% who received ruxolitinib alone. Spleen volume reduction was sustained, with 47% of patients on the combination achieving SVR35 at week 36 compared to 23% who received ruxolitinib alone.

Symptoms: Similar symptom improvement from baseline was observed in patients who received the combination of selinexor plus ruxolitinib compared to ruxolitinib alone as measured by Abs-TSS at week 24. Patients who received the combination reported a 9.89 point improvement in Abs-TSS compared to a 10.86 point improvement in patients who received ruxolitinib alone.

Overall Survival: Promising OS signal was observed in patients who received the combination of selinexor plus ruxolitinib compared to ruxolitinib alone with a hazard ratio of 0.43 (95% CI [0.19, 1.00] nominal one-sided p=0.0222). The Company intends to continue to follow OS to maturity to further evaluate this signal.

Overall Survival Associated with SVR35: Post-hoc landmark analyses at ​weeks 12 and 24 suggest ​SVR35 may predict​ overall survival.

Variant Allele Frequency (VAF) Reduction: Evidence of potential disease modification from a pre-specified exploratory endpoint was observed at week 24 from baseline in the combination arm as 32% of patients who received the combination achieved a ≥20% reduction in VAF for JAK2, MPL, and CALR compared to 24% of patients who received ruxolitinib alone (n=261).

Other Secondary and Exploratory Endpoints: Across other secondary and exploratory endpoints of progression-free survival, hemoglobin stabilization, and bone marrow fibrosis improvement, no meaningful difference was observed between the trial arms as of the data cut-off of February 20, 2026. The Company intends to further evaluate these endpoints as they mature.

Patients were randomized 2:1 to 60 mg of selinexor once weekly plus ruxolitinib or placebo plus ruxolitinib. The ruxolitinib dose was determined based on the patients’ baseline platelet count per the drug’s prescribing information. All data presented are as of the data cut-off of February 20, 2026.

“The results from SENTRY are an important development for patients as the combination of selinexor plus ruxolitinib meaningfully improved spleen response and we observed a promising signal in overall survival. Reducing spleen volume remains one of the most important treatment goals in myelofibrosis since achieving SVR35 is associated with improvement in overall survival,” said Dr. John Mascarenhas, Professor of Medicine at the Icahn School of Medicine at Mount Sinai and Director of the Center of Excellence for Blood Cancers and Myeloid Disorders. “While the symptom endpoint did not reach statistical significance, patients treated in both arms achieved similar symptom improvement relative to baseline. Importantly, while JAK inhibitors have been the backbone of therapy, continued progress requires new therapies that target additional biological pathways. Inhibition of XPO1 represents a differentiated mechanism that has the potential to address these pathways and evolve treatment beyond JAK inhibition alone.”

“For patients with myelofibrosis, improvements in spleen and symptoms are expected outcomes from JAK inhibitors such as ruxolitinib. The SENTRY topline results suggest that the combination of selinexor and ruxolitinib delivers superior spleen reduction, which may predict overall survival, while offering similar symptom improvement, and may offer an important advance for our patients,” said Dr. Claire Harrison, Professor of Myeloproliferative Neoplasms and Deputy Chief Medical Officer of Research, Data, and Analytics at Guy’s and St. Thomas’ NHS Foundation Trust in the United Kingdom.

“Selinexor’s differentiated mechanism provides a complementary approach to JAK inhibition and highlights the importance of targeting additional biological pathways beyond JAK signaling to further advance outcomes for patients with myelofibrosis. I am encouraged by the speed and magnitude of spleen response, and the promising overall survival signal and evidence of potential disease modification. In totality, these data underscore selinexor’s potential to meaningfully improve clinical outcomes for patients with myelofibrosis,” said Reshma Rangwala, MD, PhD, Chief Medical Officer and Head of Research of Karyopharm. “On behalf of Karyopharm, I would like to thank the patients, families, caregivers, investigators, and clinical trial team who participated in this trial. We are excited to share our results with regulatory authorities, key opinion leaders and patient advocacy organizations.”

“The myelofibrosis community is waiting for new treatment options that can build upon the benefit of JAK inhibitors. Improving overall survival is the ultimate goal for people living with myelofibrosis and I am incredibly encouraged by these results,” said Kapila Viges, Chief Executive Officer of the MPN Research Foundation. “These results are an exciting development for the myelofibrosis community.”

The combination demonstrated a manageable safety and tolerability profile consistent with the known profile of selinexor and ruxolitinib individually. No new safety signals were observed.

The five most common all-grade treatment emergent adverse events (TEAEs) in the selinexor plus ruxolitinib arm were thrombocytopenia (selinexor plus ruxolitinib arm: 59%; placebo plus ruxolitinib arm: 43%), anemia (57%; 58%), nausea (57%; 17%), constipation (32%; 36%) and neutropenia (27%; 9%) (n=234; n=116). The rate of grade 3+ TEAEs was 70% in the selinexor plus ruxolitinib arm compared to 50% in the placebo plus ruxolitinib arm. The rate of TEAEs leading to treatment discontinuation was 15% in the selinexor plus ruxolitinib arm and 9% in the placebo plus ruxolitinib arm. The rate of confirmed leukemic transformations was the same across both arms of the trial at 1.7%.

The Company will be meeting with the U.S. Food and Drug Administration (FDA) to discuss the totality of the data from the SENTRY trial and its supplemental new drug application (sNDA) filing plan.

The Company plans to share additional data from the Phase 3 SENTRY trial at an upcoming medical meeting and expects to submit a manuscript to a peer-reviewed medical journal. The Company believes that potential inclusion in relevant compendia could occur in the second half of 2026.

SENTRY (XPORT-MF-034; NCT04562389) is a Phase 3 clinical trial evaluating a once-weekly dose of 60 mg of selinexor in combination with ruxolitinib compared to placebo plus ruxolitinib in JAKi-naïve myelofibrosis patients with platelet counts >100 x 10⁹/L. Patients were randomized 2-to-1 to the selinexor arm. The co-primary endpoints for this trial are spleen volume reduction ≥ 35% (SVR35) at week 24 and the average change in absolute total symptom score (Abs-TSS) over 24 weeks relative to baseline.

Myelofibrosis is a rare blood cancer that affects approximately 20,000 patients in the United States and 17,000 patients in the European Union¹. The disease causes bone marrow fibrosis (scarring in the bone marrow), which makes it difficult for the bone marrow to make healthy blood cells, splenomegaly (enlarged spleen), progressive anemia which often leads to symptoms like fatigue and weakness, and other disease associated symptoms including abdominal discomfort, pain under the left ribs, early satiety, night sweats and bone pain. The only approved class of therapies to treat myelofibrosis are JAK inhibitors, including ruxolitinib.  

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 in the U.S. and marketed by Karyopharm 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; (ii) in combination with dexamethasone in adult patients with heavily pre-treated multiple myeloma; and (iii) under accelerated approval in adult patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. 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, including in myelofibrosis and endometrial cancer.

Karyopharm Therapeutics Inc. (Nasdaq: KPTI) is a commercial-stage pharmaceutical company whose dedication to pioneering novel cancer therapies is fueled by a belief in the extraordinary strength and courage of patients with cancer. Since its founding, Karyopharm has been an industry leader in oral compounds that address nuclear export dysregulation, a fundamental mechanism of oncogenesis. Karyopharm’s lead compound and first-in-class, oral exportin 1 (XPO1) inhibitor, XPOVIO (selinexor), is approved in the U.S. and marketed by the Company in three oncology indications. It has also received regulatory approvals in various indications in 50 ex-U.S. territories and countries, including the European Union, the United Kingdom (as NEXPOVIO) and China. Karyopharm has a focused pipeline targeting indications in multiple high unmet need cancers, including in multiple myeloma, endometrial cancer, myelofibrosis, and diffuse large B-cell lymphoma (DLBCL). For more information about our people, science and pipeline, please visit www.karyopharm.com, and follow us on LinkedIn and on X at @Karyopharm.