Selinexor Receives FDA Fast Track Designation in Myelofibrosis
Selinexor plus ruxolitinib is under investigation as a treatment for JAK inhibitor-naïve patients with myelofibrosis as part of the phase 3 XPORT-MF-034 trial.
Investigators of the double-blind randomized phase 3 XPORT-MF-034 trial plan to enroll up to 306 patients with intermediate or high-risk myelofibrosis.
The FDA has granted fast track designation to selinexor (Xpovio) for managing myelofibrosis, including primary myelofibrosis, post–polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis, according to a press release from Karyopharm Therapeutics.1
Selinexor is currently under evaluation in combination with ruxolitinib (Jakafi) for JAK inhibitor-naïve patients with myelofibrosis as part of the phase 3 XPORT-MF-034 trial (NCT04562389). Investigators expect to have a readout of topline data from the phase 3 trial in 2025, and developers plan to assess selinexor in combination with other agents across different JAK inhibitor–naïve settings.
“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,” Reshma Rangwala, MD, PhD, chief medical officer at Karyopharm, said in the press release. “We look forward to continued interaction with the FDA as we advance the development of this promising treatment for patients in need.”
Investigators previously presented data from the phase 1 portion of the XPORT-MF-034 trial at the American Association for Cancer Research (AACR) 2023 Annual Meeting, the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, and the 2023 European Hematology Association (EHA) Congress. As of the April 10, 2023 data cutoff, 91.7% of evaluable patients treated with selinexor plus ruxolitinib achieved a spleen volume response of at least 35% (SVR35), and 77.8% experienced a symptom score improvement of at least 50% (TSS50) at 24 weeks.2 The corresponding rates in the intent-to-treat population were 78.6% and 58.3%, respectively.
All evaluable patients experienced SVR35 responses at any time, and these benefits extended to subgroups including male patients and those who received ruxolitinib at a low dose. Moreover, investigators observed improvements in major spleen and cytokine-related symptoms in all Myelofibrosis Symptom Assessment Form domains.
Any-grade treatment-emergent adverse effects (TEAEs) among patients receiving 60 mg of selinexor plus ruxolitinib included nausea (78.6%), anemia (64.3%), thrombocytopenia (64.3%), and fatigue (57.1%). Grade 3 or higher TEAEs included anemia (42.9%), thrombocytopenia (28.6%), and back pain (14.3%). Most instances of nausea were grade 1 (75%) and did not result in any treatment-related discontinuations.
“The substantial degree of spleen volume reduction observed across all subgroups with selinexor…in combination with ruxolitinib is very encouraging,” principal investigator John Mascarenhas, MD, 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, said in a press release at the time these data were published.
Investigators of the double-blind randomized phase 3 XPORT-MF-034 trial plan to enroll up to 306 patients with intermediate or high-risk myelofibrosis. Patients will be randomly assigned 2:1 to receive 60 mg of selinexor or matched placebo orally on days 1, 8, 15, and 22 of each 28-day cycle plus 15 or 20 mg of ruxolitinib twice a day.
The primary end points of the trial are SVR35 and TSS50. Secondary end points include anemia response, the maximum plasma concentration of selinexor, and safety.
Patients 18 years and older with a diagnosis of primary myelofibrosis, post-essential myelofibrosis, or post-polycythemia vera myelofibrosis based on 2016 World Health Organization classification of myeloproliferative neoplasms are eligible to enroll on the trial. Additional eligibility criteria include having an ECOG performance status of 0 to 2, adequate liver function, and an estimated life expectancy of greater than 6 months.
References
- Karyopharm receives FDA fast track designation for selinexor for the treatment of myelofibrosis. News release. Karyopharm Therapeutics Inc. July 17, 2023. Accessed July 19, 2023. https://shorturl.at/loxRU
- Karyopharm initiates pivotal phase 3 study of XPO1 inhibitor selinexor and ruxolitinib in JAK inhibitor (JAKi) naïve myelofibrosis. News release. Karyopharm Therapeutics Inc. June 28, 2023. Accessed July 19, 2023. https://shorturl.at/emWY0
