Karyopharm: 'successful' outcome from Phase 2 portion of Phase 2/3 SEAL study
Karyopharm reported a successful outcome from the Phase 2 portion of the SEAL study evaluating the activity of selinexor, the company's lead, novel, oral Selective Inhibitor of Nuclear Export / SINE compound, in 57 patients with previously treated, advanced unresectable dedifferentiated liposarcoma. For the SEAL study's primary endpoint of progression-free survival, or PFS, oral selinexor showed superiority over placebo, achieving a hazard ratio, or HR, of 0.60, representing a 40% reduction in the risk of progression or death. PFS was assessed by Independent Central Radiological Review, or ICRR, based on RECIST v1.1. In this randomized, blinded Phase 2 portion of the study, oral selinexor demonstrated an expected and manageable safety profile, primarily with nausea, anorexia and fatigue, low levels of Grade 3/4 cytopenias, and no new or unexpected safety signals identified. The majority of treatment-related adverse events, or AEs, were low grade and reversible with dose modifications and/or standard supportive care. Importantly, the incidence of infections in the selinexor arm was less than that reported in the placebo arm. Additional efficacy assessments included PFS by World Health Organization, or WHO, response criteria, effects on metabolic parameters via PET Scans, and PFS according to Choi Criteria. PFS per WHO criteria achieved a HR of 0.84; the WHO response criteria will not be included as part of the Phase 3 study objectives. Karyopharm intends to submit detailed results from the Phase 2 portion of the SEAL study for presentation at a future medical meeting.