An oral formulation of AC480 has been evaluated in multiple Phase 1/2 clinical trials and a recently completed Phase 2 clinical trial. At doses up to 600 mg/day, investigator assessments of efficacy in solid tumors across completed Phase 1 clinical trials indicated 25 (42%) patients had stable disease from three to 14 months and 17 patients (30%) had stable disease greater than five months. Most treatment-related adverse events were mild to moderate in severity, and included nausea, vomiting, diarrhea, fatigue, cough, elevation of the liver enzymes, and rash.
Oral AC480 was also evaluated in a Phase 2, open-label, dose-ranging and efficacy trial in advanced relapsed/refractory solid tumors. Results indicate that oral AC480 is generally well tolerated in patients taking a total of up to 600 mg/day administered on a twice-daily (BID) schedule with food. Of the 26 patients treated, 62% had stable disease.
A Phase 1 clinical trial is underway to evaluate oral AC480 in patients with relapsed glioblastoma multiforme (GBM) who are suitable for further surgical resection of their tumors. Data suggests a role for HER receptors in brain tumors, but results reported for Tarceva indicate poor penetration of the drug into the tumor. This Phase 1 clinical trial is evaluating oral AC480 administered at 300 mg BID. The objective of this study is to explore the intra-tumoral and plasma pharmacokinetics of oral AC480 and to evaluate the anti-proliferative activity of oral AC480 after two weeks of dosing, determined by PET scan prior to and at the time of surgery and by CT scanning post-surgery while patients are maintained on oral AC480.
This Phase 1 clinical trial has enrolled five patients and preliminary data indicate that AC480 is present in surgically resected GBM tumors at significantly higher concentration than in plasma. If these results are confirmed in a Phase 2 GBM trial, oral AC480 may have utility in the treatment for both GBM and brain metastases which express epidermal growth factor receptor (EGFR), such as breast and non-small cell lung cancer (NSCLC).