An intravenous (IV) formulation of AC480 was developed to test the hypothesis that high, pulsatile doses of a HER inhibitor administered in combination with chemotherapeutic agents, such as taxanes, can have significant anti-tumor activity. Published data with oral HER inhibitors administered intermittently in combination with taxanes, such as docetaxel and abraxane, demonstrate significant activity in clinical studies. These clinical data are supported by preclinical data showing that combining HER inhibitors with taxanes produces synergistic anti-tumor activity. However, currently-approved oral HER inhibitors, such as Tarceva and Tykerb, are difficult to administer at the high doses required to show this synergy. Such dosing regimens could involve ingesting more than twenty tablets per day, which may not be adequately absorbed. AC480 IV is the only intravenous formulation of a pan-HER inhibitor in development suitable for delivering high, pulsatile doses in combination with taxanes.
The AC480 IV IND was filed in April 2010. In the fourth quarter of 2010 we initiated a Phase 1 clinical trial of AC480 IV as monotherapy and in combination with docetaxel in patients with advanced solid tumors, including lung and breast cancer.