AMG 386: profile of a novel angiopoietin antagonist in patients with ovarian cancer

Abstract

Introduction: Ovarian cancer is the second most common gynecologic malignancy in the world with the majority of women presenting with advanced disease; whilst chemotherapeutic advances have improved progression-free survival, the increases in overall survival have been marginal. Novel biologic agents, including those designed to disrupt tumor angiogenesis, have demonstrated promising antitumor activity.

Areas covered: This review evaluates AMG 386, a novel investigational angiopoietin antagonist peptide-Fc fusion protein (peptibody), which potently and selectively inhibits angiopoietin-1 and angiopoietin-2 binding to the Tie2 tyrosine kinase receptor. Preclinical and clinical studies for AMG 386 are summarized, highlighting data pertaining to ovarian cancer. The role of angiopoietins in regulating physiologic and tumorigenic angiogenesis is addressed, as well as a brief discussion of non-angiopoietin anti-angiogenic strategies, followed by a review of preclinical, Phase I and II data and ongoing clinical studies for AMG 386, all in the context of ovarian cancer.

Expert opinion: AMG 386 has clinical activity and an acceptable safety profile both as monotherapy and in combination with chemotherapy. Of note, as the toxicity profiles of AMG 386 and inhibitors of the VEGF axis do not substantially overlap, AMG 386 could potentially be combined with other anti-angiogenic compounds to maximize disruption of malignant vascularization in ovarian cancer and other solid tumors.

Keywords::

• AMG 386
• angiopoietin
• anti-angiogenesis
• ovarian cancer
• peptibody
• targeted therapy

Notes