A randomized double-blind phase II study of the combination of oral WX-671 plus capecitabine versus capecitabine monotherapy in first-line HER2-negative metastatic breast cancer (MBC).

508 Background: uPA and its inhibitor PAI-1 play a key role in tumor invasion, metastasis and tumor growth. uPA and PAI-1 are biomarkers validated at highest level of evidence in breast tumors and are recommended for clinical decision making by ASCO. WX-UK1 is a competitive inhibitor of uPA with an inhibition constant in the submicromolar range. WX-671 (upamostat) is an oral prodrug of WX-UK1. Methods: Female patients aged >18, with HER2 negative MBC were randomized in a double-blind fashion to receive upamostat (200 mg orally daily for 21 days) plus C (1000 mg/m2 orally twice daily for 14 days) vs. C (same regimen) in 3 week treatment cycles until progressive disease or unacceptable toxicity. 132 from five countries were enrolled. The primary objective was to evaluate the efficacy of the combination of upamostat and C compared to C alone by assessment of progression free survival (PFS). The study also evaluated the objective response rate and safety as well as pharmacokinetics (PK). Efficacy was evaluate...