Profile of bavituximab and its potential in the treatment of non-small-cell lung cancer

Abstract

Irene Stasi, Federico Cappuzzo Medical Oncology Department, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy Abstract: Bavituximab is a an unconjugated, chimeric immunoglobulin G1 (IgG1) monoclonal antibody directed against the phosphatidylserine (PS) expressed on tumor endothelium, with a specific mechanism of action. PS is an anionic membrane phospholipid, physiologically restricted to the internal membrane leaflet; various pathophysiologic processes cause the exposure of PS on the external membrane leaflet. Bavituximab, once bound, starts up host effector activities, such as antibody dependent cellular cytotoxicity, causing vessel destruction and enhancing antitumor immunity. Phase I clinical trials of bavituximab administered as monotherapy or in combination with other chemotherapeutic agents in adults with pretreated solid tumors have been accomplished, indicating that bavituximab can be safely dispensed weekly, with a recommended dose of 1 and 3 mg/kg. A Phase II randomized, placebo-controlled trial of bavituximab plus docetaxel, in the second-line therapy setting of locally advanced or metastatic non-small-cell lung cancer, has been conducted and recently presented, suggesting a clinical benefit of the combination, with an overall response rate of 17% and median overall survival of more than 11 months. A Phase III trial is currently ongoing. Bavituximab has been studied in combination with platinum-based doublets with promising results. In the present paper we summarize the preclinical development and clinical experience with bavituximab in non-small-cell lung cancer. Keywords: bavituximab, NSCLC, targeted therapy, vascular disrupting agent, vascular targeting agent