AVEO’s ficlatuzumab-gefitinib Phase 1b/2 trial data against NSCLC to be presented at ASCO 2011

AVEO Pharmaceuticals, Inc. (NASDAQ: AVEO) today announced results from the Phase 1b portion of its Phase 1b/2 clinical study of ficlatuzumab in combination with gefitinib (Iressa™) in Asian subjects with non-small cell lung cancer (NSCLC). Ficlatuzumab is AVEO's lead monoclonal antibody candidate and a potent HGF/c-MET pathway inhibitor, and these results show that ficlatuzumab was well tolerated and demonstrated clinical activity in patients with NSCLC when combined with gefitinib. The Phase 1b results as well as an update on the ongoing Phase 2 portion of the trial will be featured as poster presentations during the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO), abstract numbers 7571 and TPS213 respectively.

Tony Mok, M.D., professor, Department of Clinical Oncology, The Chinese University of Hong Kong, and senior investigator of the Phase 1b/2 trial commented, "The Phase 1b data show that the combination of ficlatuzumab and gefinitib demonstrated promising clinical activity and was well tolerated in patients. These data are encouraging as we continue to evaluate ficlatuzumab in combination with gefinitib in patients with both wild-type and mutant EGFR NSCLC in the ongoing Phase 2 trial."

Overview of the Clinical Trial

This Phase 1b/2 clinical trial is designed to test the activity of ficlatuzumab in combination with gefitinib in first-line treatment of Asian subjects with NSCLC. During the Phase 1b portion, there was a dose escalation of ficlatuzumab (first cohort of three patients received 10 mg/kg and second cohort of twelve patients received 20 mg/kg intravenously every two weeks) in combination with gefitinib (250 mg once-daily, oral for full four week cycle) in 15 Asian patients with NSCLC. The objective was to determine the safety, tolerability, dose-limiting toxicity (DLT), and recommended dose of ficlatuzumab in combination with gefitinib for the Phase 2 portion (RP2D). All patients were pre-treated with chemotherapy and ten patients had prior treatment EGFR tyrosine kinase inhibitors (TKI). With a median duration of treatment of 14 weeks among patients in the RP2D cohort, key findings include:

• No DLTs were observed in the dose-escalation cohorts
• RP2D is ficlatuzumab 20 mg/kg intravenously every two weeks combined with gefitinib 250 mg once-daily, orally
• The combination of ficlatuzumab and gefinitib was well tolerated and demonstrated clinical activity in patients with NSCLC
• Out of the 12 patients in the RP2D cohort, five patients (all of whom had no prior EGFR TKI therapy) experienced a partial response and four patients experienced stable disease.

"These Phase 1b results demonstrate the combinability of ficlatuzumab with an established anti-cancer agent and suggest the potential for efficacy of such a combination in NSCLC, one of the most devastating and difficult to treat cancers," said Tuan Ha-Ngoc, president and chief executive officer of AVEO. "We are pleased to report we have recently completed patient enrollment in the ongoing Phase 2 portion of this trial evaluating ficlatuzumab in combination with gefitinib as first-line therapy for patients with wild-type and mutant EGFR NSCLC. We anticipate top-line data from the Phase 2 portion of the trial in 2012."

The Phase 2 portion of the study began after determination of the RP2D in the dose-escalating Phase 1b portion and in parallel with the Phase 1b safety expansion. The open-label, two-arm, randomized Phase 2 study is designed to compare the combination of ficlatuzumab and gefitinib versus gefitinib monotherapy, in clinically selected Asian subjects with previously untreated advanced NSCLC who have a high likelihood of harboring activating EGFR mutations. Subjects who demonstrate disease control (complete response, partial response, or stable disease for 12 weeks or longer) in the gefitinib alone arm will cross-over upon progression to a combination of gefitinib and ficlatuzumab to assess whether acquired resistance to gefitinib can be overcome with the addition of ficlatuzumab. Although molecular markers are not required for study entry, tumor tissue has been obtained from the majority of patients for biomarker and correlative studies.