Abstract B295: A Phase Ib study of bavituximab plus carboplatin and pemetrexed in chemotherapy-naïve incurable stage IIIb/IV non-squamous non-small cell lung cancer.
Authors: Grilley-Olson Juneko E. , Villaruz Liza C. , Stinchcombe Thomas E. , Weiss Jared , Shan Joseph , Vashishtha Anshu , Ivanova Anastasia , Socinski Mark A. 
Published: August 2014

Abstract
Background: Bavituximab (B) is a phosphatidylserine (PS) targeting monoclonal antibody that modulates the tumor microenvironment from a primarily immunosuppressive state to an immune activating state. PS exposure in the tumor microenvironment is immunosuppressive, and increases in response to chemotherapy, radiotherapy and oxidative stress. B has been shown to overcome immune suppression and stimulate antitumor immunity in preclinical models. A randomized phase II study of B in combination with docetaxel showed a 60% improvement in median OS in second line NSCLC, and a phase III trial is planned. We report on B in combination with pemetrexed (P) and carboplatin (C), in treatment naïve locally advanced or metastatic non-squamous NSCLC.
Methods: We conducted an open-label, single arm phase Ib study (standard 3+3 design) of B (0.3mg/kg, 1mg/kg, and 3mg/kg) with fixed dose with C (AUC 6) plus P (500mg/m2) q3wks x maximum 6 cycles, with optional maintenance B until disease progression. Primary objectives are to characterize the safety, determine dose limiting toxicities (DLT), and establish the recommended phase 2 dose (RP2D). Secondary objectives include determining ORR and PFS. At the MTD, up to 16 patients (pts) are enrolled to further characterize safety and preliminary evidence of efficacy, incorporating an early stopping rule based on an excessive proportion of DLTs observed. DCE-MRI at baseline and end of cycle 1 was explored as a potential pharmacodynamic biomarker.
Results: Currently 21 of 25 pts have received at least one dose of CPB (48% female, 90% white), median age of 53 (range 43-73y). Most commonly reported drug-related AEs (&gt;10%), include (all %; G3/4%): anemia (62; 10), fatigue (48; 10), nausea (48; 5), thrombocytopenia (43; 29), neutropenia (38; 19), vomiting (38; 19), ALT and AST increase each (29; 0), anorexia (24; 5), thromboembolic event (19; 19), diarrhea (19; 0), rash (19; 0), leukopenia (14; 10), hyponatremia (14; 5), edema (14; 0), insomnia (14; 0), skin disorder (14; 0). No DLTs have been reported. 16 SAEs have been reported in 7 pts, of which 3 were considered related to study. As of 8/8/13, 14 completed planned 4 cycles CPB therapy; 5 came off study prior to completion due to SAEs (2 venous and 2 arterial thromboembolism, 1 hematologic toxicity), 1 due to PD, and 1 withdrew consent. 2 completed &gt;10 cycles with maintenance B. Best unconfirmed response includes 35% PR, 50% SD, 10%PD, 1 pt not available. 3 pts have completed the optional DCE-MRI biomarker imaging.
Conclusions: CPB is relatively well tolerated, with most toxicities attributable to CP. No unexpected adverse events were identified. A DLT was not identified and the RP2D is yet to be determined. Response rates reported to date are encouraging, although conclusions are limited due to the small number. Data are not sufficiently mature to report PFS and OS. Results including DCE-MRI imaging will be updated.
Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B295.
Citation Format: Juneko E. Grilley-Olson, Liza C. Villaruz, Thomas E. Stinchcombe, Jared Weiss, Joseph Shan, Anshu Vashishtha, Anastasia Ivanova, Mark A. Socinski. A Phase Ib study of bavituximab plus carboplatin and pemetrexed in chemotherapy-naïve incurable stage IIIb/IV non-squamous non-small cell lung cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B295.