A Phase I Study of Oral BMS-275291, a Novel Nonhydroxamate Sheddase-Sparing Matrix Metalloproteinase Inhibitor, in Patients with Advanced or Metastatic Cancer

Abstract

BMS-275291 is a nonhydroxamate MMP inhibitor with a novel mercaptoacyl zinc-binding group. In this study, plasma concentrations of BMS-275291 continuously exceeded in vitro MMP IC(50) values without dose-limiting joint toxicity. In this refractory patient population, a suggestion of disease stabilization was observed in 12 patients. On the basis of preclinical, clinical, and pharmacokinetic data, the recommended phase II dose for future study is 1200 mg/day.