MGCD265, a multitargeted oral tyrosine kinase receptor inhibitor of Met and VEGFR: Dose-escalation phase I study.

3039 Background: MGCD265 is a multikinase inhibitor, with nanomolar IC50 against Met, VEGFR 1, 2, and 3, Tie-2, and Ron. This spectrum may confer greater anti-tumor activity than inhibiting either target alone. MGCD265 has broad anti-tumor effects in preclinical models. Methods: Patients (pts) with advanced malignancies were enrolled in this Phase I, open-label, dose escalating study using the classic 3+3 study design. MGCD265 was administered every day over a 21-day cycle. The aim of this study is to determine the safety profile including the maximum tolerated dose and the dose limiting toxicities (DLTs) of MGCD265. The pharmacokinetic (PK), pharmacodynamic (PD) profiles and the anti-tumor activity of MGCD265 were also evaluated. Results: As of January 10, 2012, 56 patients were enrolled (M/F: 37/19; ECOG 0/1/2: 16/38/2; median age: 61 years old). MGCD265 was dose escalated from 24 mg/m2 QD to 235 mg/m2 BID with a favorable safety profile. The DLTs (n=1 for each event) captured were: grade 2 hypertension...