Karyopharm Therapeutics (NASDAQ:KPTI) today announced topline results from its global Phase 3 SENTRY clinical trial (n=353) evaluating the XPO1 inhibitor selinexor in combination with ruxolitinib (Jakafi®) for the frontline treatment of patients with myelofibrosis.
The trial yielded a divergent outcome across its co-primary endpoints, highlighting a potent physical response that did not translate into the anticipated symptomatic relief according to standard measurement scales.
The study successfully met its first co-primary endpoint of Spleen Volume Reduction of 35% or greater (SVR35) at Week 24.
Patients receiving the selinexor-ruxolitinib combination achieved an SVR35 rate of 50%, compared to 28% for those receiving ruxolitinib plus placebo (one-sided p<0.0001).
This robust reduction in splenomegaly—a hallmark of the disease—suggests that adding selinexor may significantly enhance the cytoreductive capabilities of standard JAK inhibitor therapy.
However, the trial failed to meet its second co-primary endpoint, the Absolute Total Symptom Score (Abs-TSS).
This measure tracks the reduction in debilitating disease-related symptoms like fatigue, night sweats, and bone pain.
While the combination showed activity, it did not reach a statistically significant threshold over the control arm.
Analysts suggest that the increased frequency of Grade 3+ treatment-emergent adverse events (TEAEs) in the combination arm—specifically nausea and thrombocytopenia—may have confounded the patient-reported symptom scores during the initial 24-week period.
Despite the symptom miss, Karyopharm highlighted a "highly promising" early signal in Overall Survival (OS), with an initial Hazard Ratio (HR) of 0.43.
Although the data is not yet mature, it indicates a potential long-term mortality benefit for patients on the combination therapy.
The company intends to engage with the FDA and other global regulators to discuss the totality of the SENTRY data, emphasizing the critical importance of spleen volume reduction as a surrogate for clinical benefit in this rare bone marrow cancer.