Phase 1 Study Of Jnj-42756493, A Pan-Fibroblast Growth Factor Receptor (Fgfr) Inhibitor, In Patients With Advanced Solid Tumors

2501 Background: JNJ-42756493 is an orally bioavailable FGFR 1, 2, 3 and 4 inhibitor with nanomolar antitumor activity in cell lines and in vivo models with FGFR pathway aberration. Methods: This first in human study consists of 3 parts: dose escalation part 1to determine the recommended phase 2 dose (RP2D), dose confirmation part 2 with focus on pharmacodynamic effects, and dose expansion part 3 to evaluate the antitumor activity in selected solid tumors with FGFR gene amplification, mutation or translocation at the RP2D. Biomarkers include tumor tissue genomic profiling, skin/tumor biopsies and soluble serum markers. Toxicity is graded with CTCAE-4 and antitumor activity is assessed using RECIST 1.1. Results: As of 27 January 2014, 37 patients have been treated at 6 dose levels (0.5, 2, 4, 6, 9 and 12 mg daily continuously) in part 1. Most common (≥ 20% of patients) adverse events (AEs) were hyperphosphatemia (60%), asthenia (46%), dry mouth (30%), constipation (27%), abdominal pain (22%), stomatitis (2...