Phase Ib/II Study of LY2780301 in Combination With Weekly PACLITAXEL in HER2-metastatic Breast Cancer
Status:
Terminated
Trial end date:
2018-12-12
Target enrollment:
Participant gender:
Summary
The overall rationale of this study evaluating tolerance and efficacy of LY2780301 in
combination with paclitaxel in HER2-negative, inoperable locally advanced or metastatic
breast cancer (MBC) is based on :
- the medical need in this population with either hormonal-resistant or unsensitive and/or
rapidly progressive disease
- the preclinical evidences for involvement of PI3K/AKT pathway in tumor progression and
drug resistance, including taxanes as well as its potential reversion by AKT inhibition
- the high level of frequency of PI3K/AKT activation in HER2-negative MBC
- the in vitro and in vivo preclinical activity of LY2780301, and its synergistic
combination with various anticancer agents, including taxanes
- the favourable profile of tolerance of LY2780301 in phase I trial
Weekly paclitaxel is conventionally administered at 80 mg/m²/week and is a standard treatment
in breast cancer (BC) As described above, LY2780301 500 mg once daily has been established as
the RP2D in phase I single agent trial.
Evidence of pharmacodynamic activity was noted at 400-500 mg QD. Conservatively, the first
dose level to be explored will be LY2780301 400 mg QD and paclitaxel 70 mg/m²/week.