Phase III SEAL study of Xpovio shows efficacy in liposarcoma.- Karyopharm Therapeutics

Karyopharm Therapeutics reported it will present positive results from the Phase III portion of the randomized, double blind, placebo controlled, cross-over SEAL study evaluating single agent, oral Xpovio (selinexor) versus matching placebo in patients with liposarcoma. As previously reported, the SEAL study met its primary endpoint of a statistically significant increase in median progression-free survival (PFS) in patients with advanced unresectable dedifferentiated liposarcoma following at least two prior therapies. The median PFS in the Xpovio arm of the Phase III portion of the SEAL study was 2.83 months compared to 2.07 months in the placebo arm (hazard ratio (HR)=0.70; p=0.023). These data indicate that treatment with Xpovio reduced the risk of disease progression or death by approximately 30%, compared to placebo. The estimated 6-month PFS survival probability was 23.9% on the selinexor arm compared to 13.9% on placebo. Additionally, the 12-month PFS survival probability was 8.4% on the selinexor arm compared to 2% on the placebo arm. Finally, 7.5% of patients on the selinexor arm had a 15% or greater reduction in their disease burden as measured by target lesion size while none of the patients on the placebo arm achieved this level of reduction. The trial allowed patients on placebo with objective progression to cross over to the Xpovio treatment arm. The median overall survival for patients who received Xpovio was 9.99 months compared to 9.07 months for patients who never crossed over to the Xpovio treatment arm (HR=0.69; p=0.122). The most common treatment-related adverse events (AEs) were cytopenias, along with gastrointestinal and constitutional symptoms and were consistent with those previously reported from other selinexor studies. Data were reported at the Connective Tissue Oncology Society 2020 Annual Meeting (CTOS 2020).