Phase I study of the safety and efficacy of INC280 in patients with advanced MET-dependent solid tumors.

2520^ Background: Aberrations in the MET receptor tyrosine kinase pathway occur in various human malignancies (via MET amplification, mutation, or overexpression) driving cell proliferation, survival and metastasis. INC280 is a highly selective, oral small molecule MET inhibitor with preclinical activity in human tumor models. This dose escalation study evaluated INC280 in patients (pts) with MET dependent advanced solid tumors. Methods: In this Phase (Ph) I study, the primary objective was to determine the MTD or recommended Ph II dose (RP2D), safety and tolerability of INC280; secondary objectives included preliminary antitumor activity and PK. Eligible pts (aged ≥18 years, ECOG PS ≤2) had tumors that were refractory to current therapy or for which no effective therapy exists, and confirmed MET dysregulation (by FISH or IHC). An adaptive Bayesian logistic regression model guided dose escalation in establishing the MTD/RP2D. Results: As of December 2, 2013, 33 pts were enrolled in the dose-escalation par...