Karyopharm Therapeutics (KPTI) Study result summary

Study background and rationale

• Phase III SENTRY trial evaluated selinexor plus ruxolitinib in JAK inhibitor-naive myelofibrosis patients, presented at ASCO and published in JCO.

• Myelofibrosis treatment has relied on JAK inhibitors, but these have limitations in spleen reduction and survival benefit.

• SENTRY aimed to address unmet needs by combining selinexor, an XPO1 inhibitor, with ruxolitinib to enhance disease modification and outcomes.

• The trial included global enrollment, randomizing 353 patients 2:1 to selinexor plus ruxolitinib versus placebo plus ruxolitinib.

• Co-primary endpoints were spleen volume reduction (SVR35) and symptom score improvement at week 24.

Study design and patient population

• Global, double-blind, randomized, placebo-controlled Phase 3 trial in JAK inhibitor-naïve myelofibrosis patients.

• Baseline characteristics, including age, sex, risk, and molecular profile, were well balanced between arms.

• Median follow-up was approximately 11–12 months at data cutoff.

Key efficacy results

• Selinexor plus ruxolitinib nearly doubled the rate of SVR35 at week 24 (49.8% vs 28.0%, OR 2.58, P<0.0001), with benefit sustained through week 36.

• Mean spleen volume reduction at week 24 was 40.0% for the combination versus 26.7% for ruxolitinib alone.

• Spleen volume reduction was rapid, deep, and sustained, with benefits evident as early as week 12 and maintained through week 36.

• Symptom improvement was comparable between arms, with no significant difference in total symptom score change.

• Early survival signal observed, with a hazard ratio of 0.43 and >50% reduction in risk of death for the combination arm at median follow-up of ~12 months.

• SVR35 at week 24 correlated with improved overall survival.