Phase 1, first-in-human study of ARQ 087, an oral pan-Fibroblast Growth Factor Receptor (FGFR) inhibitor, in patients (pts) with advanced solid tumors.

2545 Background: ARQ 087 is a novel, orally bioavailable, ATP-competitive inhibitor of multiple kinases, including FGFR1-3. It has potent in vitro and in vivo inhibitory effects on a variety of human tumor cell lines and xenograft models dependent on FGFR signaling. Methods: This first-in-human 2-step study was initiated in pts with advanced solid tumors. Step 1: dose escalation/food-effect to characterize PK, safety, maximum tolerated and recommended Phase 2 Dose (RP2D; unselected for FGFR aberration). Step 2: expansion cohort to to assess safety and clinical activity of ARQ 087 in selected tumor types, including FGFR gene amplification, translocation and mutation. Assessments included tumor molecular status, response by RECIST v.1.1 every 8 weeks (wks), plasma concentrations of FGF19, 21, 23, fasting glucose and phosphate. Results: 61pts were treated (dose range 25-425mg QOD or QD) in Step 1; the majority were female (61%), mean age 64 yrs (34 -78). The RP2D was defined as 300 mg QD continuous dosing. D...