Phase I, dose-finding study of monotherapy with AZD8931, an inhibitor of ErbB1, 2, and 3 signaling, in patients (pts) with advanced solid tumors.

3097 Background: AZD8931 is an oral, equipotent inhibitor of ErbB1, ErbB2 and ErbB3 receptor signaling. Methods: This open-label, multiple ascending (standard 3+3 design) dose cohort study (NCT00637039) determined the safety, tolerability, and PK of AZD8931. Pts received a single oral dose of AZD8931 followed by a 4-day observation and then AZD8931 bid for 21 consecutive days (continuation post day 21 was optional). Results: 28 pts (mean age 56 years) received AZD8931 (n=5, 40 mg bid; n=8, 80 mg bid; n=6, 160 mg bid; n=6, 240 mg bid; n=3, 300 mg bid); 21 had metastatic disease and 27 had received prior cancer therapy. The most common primary tumors were ovary (n=8) and breast (n=5). The 21-day repeat-dosing period was completed by 22 pts and 9 remained on treatment after this period. Median duration of exposure to AZD8931 was 22 days (range 7–140). DLTs were identified in 1/6 pts in the 240 mg bid cohort (Grade [Gr] 3 rash) and in 2/2 evaluable pts in the 300 mg bid cohort (Gr 3 and Gr 4 diarrhea). Skin a...