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ARRY–380 – HER2 Program for Cancer
ARRY-380 is an orally active, reversible and selective HER2 inhibitor. HER2, also known as ErbB2, is a receptor tyrosine kinase that is over-expressed in breast cancer and other cancers such as gastric and ovarian cancer. In multiple preclinical tumor models, ARRY-380 was well tolerated and demonstrated significant dose-related tumor growth inhibition that was superior to Herceptin® (trastuzumab) and Tykerb® (lapatinib). Additionally, in these models, ARRY-380 was well tolerated and additive for tumor growth inhibition when dosed in combination with the standard of care therapeutics Herceptin or Taxotere® (docetaxel).
In December 2010, Array presented positive interim results of ARRY-380 in a Phase 1 trial in patients with advanced cancer at the San Antonio Breast Cancer Symposium. Interim results were presented on 19 patients with HER2-positive cancer evaluable for response who were treated with ARRY-380 at doses greater than or equal to 200 mg (twice daily). All of the HER2-positive metastatic breast cancer patients had been previously treated with Herceptin and 81% were previously treated with Tykerb. Thirty two percent of the 19 patients had clinical benefit as measured by a partial response or stable disease for six months or longer. Fifteen of the 19 patients had measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST); of these patients, seven had regressions in target lesions. Of the four patients with no measurable disease, three had regressions of non-target chest wall lesions. ARRY-380 demonstrated an acceptable safety profile; the predominant treatment related adverse events have been Grade 1. Because ARRY-380 is selective for HER2 and does not inhibit EGFR, there was, as expected, a low incidence and severity of diarrhea, rash and fatigue. Additionally, there were no Grade 4 treatment related adverse events or treatment related cardiac events reported. The maximum tolerated dose of ARRY-380 established in this Phase 1 trial is 600 mg (twice daily). An expansion cohort in patients with HER2-positive metastatic breast cancer is ongoing to confirm safety and investigate pharmacodynamic markers.
Recently, a sub-population of approximately one-third of HER2+ patients who express high level of truncated HER2 has been identified. This sub-population has been reported to have shorter progression free survival and overall survival from Herceptin based therapy as compared to patients with low expression of truncated HER2. ARRY-380 targets the intracellular kinase portion of HER2 and retains activity against the truncated HER2, making this population of patients a potentially attractive option for further drug development of ARRY-380.
During fiscal 2011, we completed the dose escalation Phase 1 trial to evaluate the safety, maximum tolerated dose and pharmacokinetics of ARRY-380 in patients with advanced cancer. The drug was shown to have good pharmacokinetics, an acceptable safety profile, and anti-tumor activity in patients who had previously received Herceptin and Tykerb. ARRY-380 is currently in an expansion portion of the Phase 1 trial to confirm safety and the recommended dose for future trials. We are seeking a partner to further advance the program.
Scientific Posters
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