open accerss: Exposure–response relationship of AMG 386 in combination with weekly paclitaxel in recurrent ovarian cancer and its implication for dose selection

Abstract

Purpose  

To characterize exposure–response relationships of AMG 386 in a phase 2 study in advanced ovarian cancer for the facilitation of dose selection in future studies. 

 .....AMG 386 (previously referred to as 2xCon4) is an investigational peptide-Fc fusion protein that mediates antiangiogenic effects by potently and selectively inhibiting the interaction of angiopoietin-1 and angiopoietin-2 with Tie2 [16]. Primary endpoint results from a phase 2 study of AMG 386 in combination with weekly paclitaxel for the treatment of recurrent ovarian cancer showed longer median progression-free survival (PFS) for patients receiving AMG 386 at 10 and 3 mg/kg once weekly (QW), compared with placebo (the data are described in the primary analysis [17]). Additional dose-exposure analyses suggested a dose–response effect across treatment arms......

Blogger's Note: stats removed for ease of reading (eg. CI):

Progression-free survival (the primary endpoint) in the phase 2 study was 7.2 months in the AMG 386 10 mg/kg QW dose group and 5.7 months  in the 3 mg/kg group, compared with 4.6 months for placebo. Results from Tarone’s test and dose-exposure analyses suggested a dose–response effect for PFS across the three arms....