HER2 and EGFR are receptor kinase targets that are over-expressed in a number of malignancies, including breast, lung, pancreas, colon and head and neck cancers. ARRY-543 is a novel, oral HER2 and EGFR inhibitor that, unlike approved HER inhibitors, targets all members of the HER family, including ErbB3, either directly or indirectly, and has potential advantages in treating tumors that signal through multiple HER family members. ARRY-543 showed promising results in preclinical tumor models that signal through multiple HER family members, as well as in preclinical models when compared to, and combined with, Herceptin (trastuzumab), Xeloda (capecitabine) and Taxotere (docetaxel) – widely used treatments for solid tumors.
In a Phase 1 trial, ARRY-543 produced prolonged stable disease in patients who have previously failed prior treatments with solid tumors. ARRY-543 was well-tolerated up to 400 mg twice daily, or BID, dosing. Systemic concentrations of ARRY-543 increased with escalating doses at all dose levels tested, providing continuous exposure over a 24-hour period. Sixty percent of patients receiving doses of 200 mg BID and higher had prolonged stable disease.
Our clinical development activities for ARRY-543 consisted of the following during fiscal 2009:
- Reported results of a Phase 1b trial in HER2-positive metastatic breast cancer, or MBC, and HER-family cancer patients showing that ARRY-543 was generally well tolerated and demonstrated evidence of tumor regression and prolonged stable disease in EGFR- and HER2-expressing cancers. Twenty one patients were evaluated: 12 had available biopsies and eight were confirmed HER2-positive. Of the confirmed patients with HER2-positive MBC treated with ARRY-543, 63 percent achieved stable disease for 16 weeks or longer. In patients with other cancers shown to express HER family members, three patients, with ovarian cancer, cervical cancer and cholangiocarcinoma, respectively, treated with ARRY-543 also achieved stable disease for 16 weeks or more; the patient with cholangiocarcinoma experienced a tumor marker response that was accompanied by a 25 percent regression of target lesions; and
- Initiated Phase 1b studies of ARRY-543 in combination with Xeloda (capecitabine), Taxotere (docetaxel) and Gemzar (gemcitabine), which are currently enrolling patients with solid tumors.
During fiscal 2010, we plan to complete the Phase 1b combination studies of ARRY-543 and to initiate a Phase 2 trial in combination with another anti-cancer drug in patients with certain gastrointestinal cancers that have dual-expressing tumors.
Scientific Posters
|
