Karyopharm begins Phase 3 clinical trial for selinexor with ruxolitinib

Karyopharm Therapeutics announced the initiation of a pivotal Phase 3 clinical trial to assess the efficacy and safety of once-weekly selinexor 60mg in combination with ruxolitinib in JAKi-naive patients with myelofibrosis. The randomized, double-blind, placebo-controlled study is expected to enroll 306 JAKi-naive patients with intermediate or high-risk myelofibrosis. Patients will be randomized 2:1 to ruxolitinib plus selinexor 60mg or ruxolitinib plus placebo in 28-day cycles. Ruxolitinib dose will be determined by the investigators based on the patients’ baseline platelet count per the drug’s prescribing information. The co-primary endpoints of the study are spleen volume response rate of greater than or equal to 35% and symptom improvement of greater than or equal to 50%at week 24, with a key secondary endpoint of anemia response at week 24. Updated data from the Phase 1 study recently presented at American Association for Cancer Research Annual Meeting 2023, American Society of Clinical Oncology 2023 and European Hematology Association 2023 showed rapid, deep and sustained spleen responses and robust symptom improvement in patients treated with selinexor 60mg in combination with ruxolitinib as of the April 10 data cut-off date. Karyopharm expects to present top-line data readout from this study in 2025. The company plans to expand its clinical development program in myelofibrosis by investigating selinexor in other front-line opportunities, such as novel combinations, to benefit the greatest number of myelofibrosis patients.