PD-019 ARQ 087, an oral pan- fibroblast growth factor receptor (FGFR) inhibitor, in patients (pts) with advanced and/or metastatic intrahepatic cholangiocarcinoma (iCCA)

Abstract

Introduction: ARQ 087 is a potent, ATP competitive pan-FGFR inhibitor with additional activity against other kinases. FGFR signaling has been implicated in the development and progression of CCA, and FGFR2 fusion has been recognized as a therapeutic target in iCCA. ARQ 087 has been tested in over 80 cancer pts. Results of the Dose Escalation portion of this study were reported previously (Papadopoulos K et al. J Clin Oncol 33, 2015; suppl, abstr 2545). Methods: This is an open-label multi-center Phase 1/2 dose escalation and signal finding study of ARQ 087. Pts were treated at 400 or 300 mg qd dose levels. Assessments included response by RECIST v1.1 every 8 weeks (wks), safety (physical examination, vital signs, ECOG PS, laboratory tests), plasma concentrations of phosphate and FGF19, 21, 23 ( potential biomarkers). Results: As of 22-Feb-16, 17 pts with iCCA were treated with ARQ 087. Mutation status by next-generation sequencing or fluorescent in situ hybridization was reported in 16 pts, including 10 pts with FGFR2 fusion. Pts were white (94%), male (47%) with ECOG PS 1 (53%) and mean age 63 yrs (39-81). Median number of previous systemic therapies was 2 (range 0-4). Drug-related adverse events (AEs; all grades) were reported in 88.2% of pts; the most common (≥10%) included fatigue (35.3%), dry mouth (29.4%), dizziness (11.8%), nausea (17.6%), ALT increased (23.5%), AST increased (17.6%), decreased appetite (17.6%), and anemia (11.8%). Twelve pts were discontinued due to: lack of clinical benefit (1), progressive disease (PD; 11). 5 pts are ongoing. Radiographic response was demonstrated in 6 pts with FGFR2 fusion: 2 confirmed partial responses (35% and 32% tumor reduction, PD at wk 24 and 40, respectively) and 2 stable diseases (25% and 18% tumor reduction, PD at wk 24 and one is ongoing). In all iCCA pts in whom FGFR2 fusion was not identified and in two pts with the fusion PD was the best response. Conclusion: ARQ 087 demonstrated manageable safety profile, with mostly G ≤2 AEs and encouraging antitumor activity in pts with iCCA with FGFR2 fusion. Part 2 of the study is ongoing.