Phase Ib Study of Bavituximab With Carboplatin and Pemetrexed in Chemotherapy-Naive Advanced Nonsquamous None-Small-Cell Lung Cancer

In this phase Ib trial we evaluated the safety, tolerability, and preliminary antitumor activity of carboplatin, pemetrexed, and bavituximab in 26 patients with advanced non-small-cell lung cancer. The combination was well tolerated with toxicities similar to pemetrexed/carboplatin alone. Introduction: Bavituximab is an immunomodulatory chimeric monoclonal antibody that inhibits phosphatidylserine signaling, which promotes innate and adaptive immune responses. In this phase Ib trial we evaluated the safety, tolerability, and preliminary antitumor activity of pemetrexed, carboplatin, bavituximab in advanced nonesmall-cell lung cancer (NSCLC). Patients and Methods: Patients with advanced nonsquamous NSCLC and performance status 0 or 1 were treated with pemetrexed 500 mg/m(2) and carboplatin area under the curve 6 once every 3 weeks for up to 6 cycles, with concurrent bavituximab (0.3, 1, or 3 mg/kg) intravenously weekly, using a standard 3+3 design. At the maximum identified dose, additional patients were enrolled to further characterize the safety profile. The primary objective was to characterize the safety, determine the dose-limiting toxicities (DLTs), and establish the recommended phase II dose of bavituximab in combination with pemetrexed and carboplatin in incurable stage IV nonsquamous NSCLC. Results: Between March 29, 2011 and December 30, 2013, 26 patients were enrolled. Three patients each were enrolled into dose escalation cohorts of bavituximab (0.3, 1, and 3 mg/kg). Therapy was well tolerated with no DLTs, and toxicities were consistent with those expected from pemetrexed/carboplatin. Overall response was 28%, with a median progression-free and overall survival of 4.8 months and 12.2 months, respectively. Conclusion: The combination of pemetrexed, carboplatin, bavituximab is well tolerated. However, with toxicities and preliminary efficacy signal similar to pemetrexed/carboplatin alone, further studies of bavituximab should focus on ways to enhance its immunomodulatory role. (C) 2018 Elsevier Inc. All rights reserved.