Karyopharm Therapeutics Inc., a commercial-stage pharmaceutical company pioneering novel cancer therapies, announced updated results from the Phase 1 portion of its study evaluating the safety and efficacy of once-weekly selinexor in combination with standard dose ruxolitinib in patients with treatment-naïve myelofibrosis (NCT04562389). The data, featured in a poster presentation at the 64th American Society of Hematology (ASH) 2022 Annual Meeting and Exposition, show that the combination of selinexor with ruxolitinib achieved rapid and sustained spleen responses, encouraging improvements in symptoms and stabilization of hemoglobin levels in patients with treatment-naïve myelofibrosis.
As of October 21, 2022, 24 patients had been assigned to either a 40 mg or 60 mg once weekly dose of selinexor, in combination with ruxolitinib 15/20 mg BID (twice daily). At week 24, 92% of efficacy evaluable patients (11 out of 12) demonstrated ≥35% reduction in spleen volume (SVR35). Ongoing reductions in SVR were seen from baseline to week 12 and week 24, with a 45% median reduction at week 12 and a 49% median reduction at week 24. 67% of the evaluable patients for symptom response (4 out of 6) at week 24 achieved ≥50% reduction (TSS50). 57% of transfusion-independent patients (13 out of 23) maintained or improved their hemoglobin levels.
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“As an oral agent with a unique mechanism of action, selinexor has previously shown single-agent activity in myelofibrosis patients,” said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. “As a result, we believe that the combination of selinexor and ruxolitinib has the potential to meaningfully build upon the current standard of care, which is ruxolitinib alone, for patients with treatment-naïve myelofibrosis. We look forward to further developing this combination in the randomized phase of the study.”
The safety population was comprised of 24 patients, all of whom received at least one dose of selinexor. The most common adverse events (AEs) were nausea (75%), anemia (62%) and fatigue (58%), the majority of which were grades 1-2. The most common reported grade 3-4 treatment-emergent AEs were anemia (37%) and thrombocytopenia (21%), both of which were reversible.
“In the Phase 1 portion of the study Karyopharm, encouraging efficacy was observed across the relevant efficacy endpoints of SVR35, TSS50, and hemoglobin stabilization and a generally manageable safety profile was observed regardless of dose. Furthermore, I find the rapid spleen reduction as early as week 12 especially notable, along with early signs of durability,” said Dr. Haris Ali, City of Hope Comprehensive Cancer Center. “These data support the potential of an oral XPO1 inhibitor, in combination with a JAK inhibitor, to deliver significant benefits for patients with myelofibrosis.”
SOURCE: PR Newswire