Phase I study of oral selective c-Met inhibitor EMD 1214063 in pts with advanced solid tumors.

2506^ Background: To perform the first-in-human study of EMD 1214063, a highly selective, reversible, ATP-competitive c-Met inhibitor that causes growth inhibition and regression of hepatocyte growth factor-dependent and -independent tumors in preclinical models. Methods: Primary objective of this dose-escalation study (3+3 design) was to establish the EMD 1214063 MTD (NCT01014936). Secondary endpoints included safety, PK, antitumor effect, and pharmacodynamics (Pd). Eligible pts had advanced solid tumors not amenable to standard therapy. Pts received once daily (QD) oral EMD 1214063 on 1 of 3 regimens (all 21-d cycles): d 1–14 followed by 7-d rest (R1), continuous 3 times weekly (R2), or d 1–21 (R3). An optimized formulation (OF) was introduced in Aug 2011. Results: 100 pts were treated (R1:42; R2:41; R3:17). On the initial formulation, doses were escalated from 30–230 mg/d in R1, and 30–115 mg/d in R2. OF data are available for 30–400 mg/d in R1, 60–175 mg/d in R2, and up to 500 mg/d in R3. Cmax and AUC...