Bavituximab is a chimeric
monoclonal antibody that targets
phosphatidylserine (PS). PS is externalized on cells in the tumor microenvironment when exposed to
hypoxia and/or other physiological stressors. On attaching to PS,
bavituximab is thought to promote antitumor immunity through its effects on PS receptors in monocytes, and myeloid-derived suppressor cells, as well as trigger antitumor effects by inducing an antibody-dependent cellular cytotoxicity on
tumor-associated endothelial cells. We conducted a phase I clinical trial of
bavituximab in combination with
paclitaxel in patients with HER2-negative metastatic
breast cancer. Patients were treated with weekly
paclitaxel (80 mg/m(2) for 3/4 weeks) and weekly
bavituximab (3 mg/kg for 4/4 weeks). Correlative studies included the measurement of circulating microparticles, endothelial cells, and apoptotic
tumor cells by flow cytometry. Fourteen patients with metastatic
breast cancer were enrolled; all were evaluable for toxicity and 13 were evaluable for response. Treatment resulted in an overall response rate (RR) of 85% with a median progression-free survival (PFS) of 7.3 months. Bone
pain,
fatigue,
headache, and
neutropenia were the most common adverse effects. Infusion-related reactions were the most common adverse event related to
bavituximab therapy. Correlative studies showed an increase in the PS-expressing apoptotic
circulating tumor cells in response to
bavituximab, but not with
paclitaxel. No changes in the number of circulating endothelial cells or apoptotic endothelial cells were observed with
therapy. Platelet and monocyte-derived microparticles decreased after initiation of
bavituximab.
Bavituximab in combination with
paclitaxel is well tolerated for treatment of patients with metastatic
breast cancer with promising results observed in terms of clinical RRs and PFS. The toxicity profile of
bavituximab is notable for manageable infusion-related reactions with no evidence for increased thrombogenicity. Recent preclinical data suggest that
bavituximab can also promote antitumor immune activity that should be explored in future clinical trials.