Safety, Tolerability, and Efficacy Study in Subjects With Advanced or Metastatic Breast Cancer

This study will determine the highest dose of KW-2450 in combination with lapatinib and letrozole that can be administered safely to subjects with advanced or metastatic breast cancer and to evaluate its effectiveness. This study was terminated in Phase 1 and never proceeded to the Phase 2 portion of the study.

This open-label, sequential, ascending, multi-dose, Phase 1/2 study will enroll up to 198 post-menopausal subjects with advanced or metastatic breast cancer whose tumors overexpress HER2. Subjects at each dose level will receive KW-2450 orally, on a continuous daily schedule in combination with lapatinib and letrozole. In the Phase 1 portion of the study, dose escalation may proceed once ≥ 3 subjects have completed Day 30. The safety of each dose level will be established prior to enrollment of subjects in the next dose level. Dose escalation will proceed sequentially. Up to 6 subjects may be enrolled at each dose level. Enrollment will proceed until the MTD has been established or the highest dose level has been reached. The Phase 2 portion of the trial will enroll 168 additional subjects. The dose level will be based on overall safety and tolerability assessments from the Phase 1 portion of the study. The subjects will be randomized into two treatment arms (1) Arm A, KW-2450 plus lapatinib plus letrozole: (2) Arm B, lapatinib plus letrozole. This study was terminated in Phase 1 and never proceeded to the Phase 2 portion of the study.