A phase 1b food effect study of the first-in-class, oral, selective inhibitor of nuclear export (SINE) selinexor (KPT-330) in patients (pts) with advanced sarcomas.

10587 Background: Sarcomas are heterogeneous diseases with multiple genetic abnormalities. XPO1 inhibition can restore the activity of multiple tumor suppressor proteins (TSP) including p53, Rb, and p27; and reduce cyclins and Akt. Selinexor is an oral XPO1 inhibitor that showed potent anti-sarcoma activity in preclinical ASPS, lipo- and bone sarcomas, and preliminary clinical activity in a phase 1 study. Methods: Oral selinexor was given at 30 mg/m2 twice weekly in capsule or tablet form based on an ongoing Phase 1. Appetite stimulants and anti-nausea agents were given. Pharmacokinetic (PK) analyses were performed under fasting and fed states (low vs high fat content). Paired tumor biopsies were obtained. Response evaluation was every 8 weeks (RECIST 1.1). All pts had documented progressive disease (PD) on study entry. Results: 16 evaluable pts (7 M/9 F; median age 55 yrs; median prior regimens: 3; ECOG PS 0/1: 11/6) including 5 leiomyo- (LMS), 4 lipo- (LPS), 3 synovial (SS), and 4 other sarcomas. Grade ...