Phase I safety and pharmacokinetic study of bavituximab, a chimeric phosphatidylserine-targeting monoclonal antibody, in patients with advanced solid tumors

Purpose: Bavituximab is a chimeric immunoglobulin G1 phosphatidylserine- targeting monoclonal antibody that triggers vascular disruption and enhances antitumor immune response. This phase I study assessed the safety and pharmacokinetics of bavituximab in patients with advanced solid tumors. Experimental Design: Patients with refractory advanced solid tumors were enrolled into four sequential dose-escalation cohorts (0.1, 0.3, 1, or 3 mg/kg bavituximab weekly) with two dosing schedules. Patients in the 0.1 and 0.3 mg/kg cohorts received bavituximab on days 0, 28, 35, and 42. Patients in the 1 and 3 mg/kg cohorts were administered bavituximab on days 0, 7, 14, and 21. Safety, pharmacokinetics, and tumor response were assessed. Results: Twenty-six patients were accrued. No maximum tolerated dose was reached. Six serious adverse events occurred in five patients, including one pulmonary embolism at 3 mg/kg, which was the only dose-limiting toxicity (DLT) in the study. Bavituximab half-life ranged from 37 to 47 hours, with no accumulation seen following administration of multiple doses. Activated partial thromboplastin time was modestly prolonged in vitro at the highest dose tested. As assessed on day 56, a total of 18 patients were evaluable for efficacy, of whom 10 had disease progression and none had an objective response. Conclusions: Bavituximab was well tolerated at doses ranging up to 3 mg/kg weekly. Pharmacokinetic studies support a weekly dosing regimen. Additional phase I and II clinical trials are in progress to investigate bavituximab in combination with chemotherapy and other molecularly targeted agents.