SENTRY phase I: Selinexor + ruxolitinib in MF

Results from the multicenter, open-label, phase I portion of the SENTRY (NCT04562389) study, evaluating selinexor, an exportin 1 (XPO1) inhibitor, in combination with ruxolitinib in patients with Janus kinase inhibitor (JAKi)-naïve myelofibrosis (MF) (N = 24), were published in Blood Advances by Ali et al. The primary endpoints were maximum tolerated dose (MTD), recommended clinical trial dose, and safety. 

Key data: No dose-limiting toxicities were observed in the 40 mg once weekly (QW) group (n = 3) or the 60 mg QW group (n = 3); no MTD was determined. Safety profiles did not significantly differ between dose groups. Grade ≥3 treatment-emergent adverse events (TEAEs) were reported in 71% of patients overall. Common TEAEs of any grade included nausea (75%), fatigue (58%), anemia (54%), thrombocytopenia (54%), constipation (38%), vomiting (38%), and headache (38%). At Week 24, spleen volume reduction ≥35% (SVR35) was demonstrated in 79% vs 40% of patients in the 60 mg QW and 40 mg QW groups, respectively. A total symptom score reduction ≥50% (TSS50) was reached in 58% of patients in the 60 mg QW group vs 40% of patients in the 40 mg QW group. The recommended phase III dose was 60 mg QW.

Key learning: Results suggest that selinexor 60 mg QW + ruxolitinib provides greater efficacy outcomes compared with selinexor 40 mg QW + ruxolitinib, with comparable safety profiles, in patients with MF; supporting 60 mg QW as the recommended phase III dose.