AMGEN'S VEGF RECEPTOR INHIBITOR SHOWED ANTITUMOR ACTIVITY

Amgen has announced results from a multicenter, single-arm, Phase II study of AMG 706, an investigational, oral, targeted VEGF receptor inhibitor. In this study, AMG 706 showed encouraging clinical activity in patients with advanced high-dose imatinib-resistant gastrointestinal stromal tumors (GIST).

In the trial 138 patients received at least one dose of AMG 706. Patients received 125 mg per day orally until progressive disease or toxicity. Independent central radiographic review confirmed 120 patients to be protocol eligible. Responses were measured using the Response Evaluation Criteria in Solid Tumors (RECIST), fluorodeoxyglucose-positron emission tomography (FDG-PET) and Choi criteria (defined as a 10 percent decrease in tumor size or a 15 percent decrease in tumor density by contrast-enhanced computed tomography scan).

The primary endpoint of the trial was objective response per RECIST assessed by an independent review. Secondary efficacy endpoints included an assessment of AMG 706 on duration of response, progression-free survival, time to progression, survival and adverse events. Additional secondary endpoints explored the utility of FDG-PET, target tumor size/density changes and assessed the pharmacokinetics.

The RECIST assessment of the 120 evaluable patients showed a clinical benefit rate of 27 percent (3 percent partial response plus 24 percent durable stable disease beyond 22 weeks). At week eight, 23 percent of patients demonstrated an objective response by FDG-PET and 33 percent showed an objective response by Choi criteria. The median progression-free survival was 16 weeks, with 26-week progression-free survival of 27 percent. Median survival was 59 weeks.

AMG 706 is an oral, highly selective inhibitor of the VEGF pathway, targeting all of the VEGF receptors that demonstrate both antiangiogenic and direct antitumor activity.