FDA Grants Fast Track Designation to Selinexor for Myelofibrosis Treatment


Phase 3 research is underway to explore the efficacy and safety of selinexor plus ruxolitinib for the treatment of myelofibrosis in adults.

  • Selinexor holds multiple indications for the treatment of hematologic malignancies in the United States, Europe, the United Kingdom, and China.

  • With a fast track designation, the development of selinexor for the treatment of myelofibrosis will be expedited.

  • The developer of selinexor, Karyopharm Therapeutics, Inc, will have continued communication with the FDA to review data and determine eligibility for priority review and rolling review of a future approval application.

The FDA has granted a fast track designation to selinexor (Xpovio) for the treatment of patients with myelofibrosis, which includes those with primary myelofibrosis, post-essential thrombocythemia myelofibrosis, and post-polycythemia vera myelofibrosis.1

Clinical development of the combination began with the phase 1/2 XPORT-MF-034 study (NCT04562389) of selinexor plus ruxolitinib (Jakafi) in myelofibrosis. Results from the study were recently presented at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting. Results showed that the combination was well-tolerated and had promising activity in terms of spleen and symptom responses.

In the phase 1/2 study, 24 patients with myelofibrosis were given selinexor 40 mg or 60 mg once daily plus standard ruxolitinib in 28-day cycles. Patients were assessed for the primary end points of maximum-tolerated dose, recommended phase 2 dose, and adverse events (AEs). The secondary end points assessed were 35% spleen volume reduction (SVR35), 50% tumor symptom score (TSS50), overall survival, anemia response, AEs, objective response rate, and pharmacokinetics.

As of the data cutoff date of April 10, 2023, 83.3% of patients in the efficacy evaluable (EE) population achieved SVR35 at week 12, 91.7% had SVR35 at week 24, and 100% had SVR35 at any time. In the intent-to-treat (ITT) population, 71.4% of patients achieved SVR35 by week 12, 78.6% achieved SVR35 by week 24, and SVR35 at any time was shown in 85.7% of patients. TSS50 at week 24 was 77.8% in the EE population, and 58.3% in the ITT population.

About the Phase 3 XPORT-MF-034 Study

Trial Name: A Phase 1/3 Study to Evaluate Efficacy and Safety of Selinexor, a Selective Inhibitor of Nuclear Export, in Combination With Ruxolitinib in Treatment-naïve Patients With Myelofibrosis

ClinicalTrials.gov Identifier: NCT04562389

Sponsor: Karyopharm Therapeutics, Inc

Recruitment Contact:
(888) 209-9326, clinicaltrials@karyopharm.com

Completion Date: March 2028

Safety findings showed that treatment-emergent AEs (TEAEs) occurred in > 25% of the study population. Grade 3 or higher TEAEs were anemia, thrombocytopenia, and back pain, which occurred in > 10% of the population. The most common any-grade TEAEs were nausea (78.6%), anemia (64.3%), thrombocytopenia (64.3%), and fatigue (57.1%).

Clinical development of selinexor for the treatment of myelofibrosis will continue with the phase 3 XPORT-MF-034 study. In the study, selinexor 60 mg will be administered in combination with ruxolitinib to patients with myelofibrosis who are naïve to JAK inhibitor (JAKi) therapy. Approximately 330 patients will be evaluated.

To be eligible, patients aged 18 years or older must have myelofibrosis with measurable splenomegaly, an ECOG performance score of 2 or lower, adequate organ function, adequate laboratory values at baseline, a life expectancy of at least 6 months, and active myelofibrosis symptoms. Patients must be ineligible for stem cell transplantation, be able to provide bone marrow biopsy during the study, and agree to use contraception during the study. Female patients must have a negative pregnancy test prior to starting study treatment.

"Fast track designation for selinexor highlights its potential to address the unmet medical need in myelofibrosis, an important acknowledgement as we continue our pivotal phase 3 study," said Reshma Rangwala, MD, PhD, chief medical officer of Karyopharm, in a press release. "Selinexor's unique mechanism of action, XPO1 inhibition, is a novel and potentially fundamental mechanism in myelofibrosis. We have been highly encouraged by the efficacy and safety data observed to date [in our phase 1 study] with selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis and believe selinexor has the potential to shift the treatment paradigm. We look forward to continued interaction with the FDA as we advance the development of this promising treatment for patients in need."


1. Karyopharm receives FDA fast track designation for selinexor for the treatment of myelofibrosis. News release. Karyopharm Therapeutics Inc. July 17, 2023. Accessed July 18, 2023. https://tinyurl.com/ye27uerh

2. Ali H, Kishtagari A, Maher K, et al. Selinexor (SEL) plus ruxolitinib (RUX) in JAK inhibitor (JAKi) treatment-naïve patients with myelofibrosis: Updated results from XPORT-MF-034. J Clin Oncol. 2023;41(suppl 16): 7063-7063. doi:10.1200/JCO.2023.41.16_suppl.7063

3. Study of selinexor in combination with ruxolitinib in myelofibrosis. ClinicalTrials.gov. Updated July 3, 2023. Accessed July 18, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04562389

Related Videos
Related Content