Description
Oncothyreon's lead compound targeting the PI-3K/AKT pathway is PX-866. Unlike other therapies that target PI-3K, PX-866 is an irreversible PI-3K inhibitor. This irreversible binding contributes to the potent in vivo activity of PX-866 relative to other reversible PI-3K inhibitors.
Preclinical studies demonstrated that PX-866 induces prolonged inhibition of tumor PI-3K signaling following both oral and intravenous administration, and has potent in vivo anti-tumor activity in human ovarian cancer, lung cancer, and intracranial glioma tumor models. PX-866 also has been shown to enhance the activity of cytotoxic agents and other targeted therapies, including gefitinib and bevacizumab, in preclinical studies.
Preliminary results of Oncothyreon's ongoing Phase 1 trial of PX-866 were presented at the American Society of Clinical Oncology Annual Meeting in May 2009. As reported at that time, 26 patients had been treated in this trial at once daily doses ranging from 0.5 mg to 10 mg. The maximally tolerated dose had not yet been identified. The most common treatment-related adverse events at the doses tested include low-grade nausea, vomiting and diarrhea. Of 24 evaluable patients, six patients with previously progressive disease had stable disease as their best response and three patients had remained on therapy. In addition, pharmacodynamic monitoring demonstrated inhibition of PI-3 kinase activity at doses as low as 1 mg per patient.
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