MGCD265, a multitargeted oral tyrosine kinase receptor inhibitor of Met and VEGFR, in combination with docetaxel.

e13604 Background: MGCD265 is a multi-target oral tyrosine kinase receptor inhibitor that targets Met, VEGFRs 1, 2, 3, Tie and Ron. The maximum tolerated dose (MTD) of MGCD265 in combination with docetaxel was initially determined using micronized tablets. MGCD265 formulation was improved and the MTD of MGCD265 in combination with docetaxel using the updated formulation was re-evaluated. Methods: Patients (pts) with metastatic or advanced solid tumors were enrolled in this Phase I, open-label, dose-escalating study to assess safety, pharmacodynamics (PD) and pharmacokinetics (PK) as well as anti-tumor activity of the combination. MGCD265 was administered every day over a 3-week cycle and docetaxel (50 then 75 mg/m2) was given intravenously once every 3 weeks (q3w). Results: As of January 11, 2012, 34 pts were enrolled (M/F: 19/15; ECOG 0/1: 19/15; median age: 64 years old). The MTD of the combination was initially defined as MGCD265 (72 mg/m2 BID)+docetaxel (75 mg/m2 q3w) based on the occurrence of dose l...