Abstract 1744: A phase Ib study of bavituximab plus carboplatin and pemetrexed in chemotherapy naive stage IV non-squamous non-small cell lung cancer
Authors: Grilley-Olson Juneko , Weiss Jared , Stinchcombe Thomas E. , Ivanova Anastasia , Tynan Maureen , Shan Joseph , Socinski Mark A. 
Published: August 2012

Abstract
Background: Bavituximab (B) is a novel chimeric IgG1 phosphatidylserine-targeting monoclonal antibody. B selective binds to phosphatidylserine complexed with β2-glycoprotein I exposed on tumor vasculature resulting in enhanced immune response and inhibition of existing as well as novel tumor vasculature. Pre-clinical data suggest a synergistic action using phosphatidylserine-targeting antibodies in combination with chemotherapy. B has previously been reported to be safe and well tolerated when given in combination with paclitaxel and carboplatin (C) in non-small cell lung cancer (NSCLC) and has produced a promising 43% overall response rate (ORR). Here, we report on the currently enrolling trial of B in combination with pemetrexed (P) and C, in treatment naïve locally advanced or metastatic non-squamous NSCLC. Methods: This is an ongoing open-label, single arm phase Ib study (standard 3+3 design) of B (0.3mg/kg, 1mg/kg, and 3mg/kg) with fixed dose CP. B is given weekly in combination with C (AUC 6) plus P (500mg/m2), given every 3 weeks, maximum of 6 cycles. Patients may elect to continue on maintenance B until disease progression. At the MTD, up to 16 additional patients will be enrolled to further characterize safety and preliminary evidence of efficacy, using an adaptive design incorporating an early stopping rule based on excessive proportion of DLTs observed. The study objectives are to determine the safety, tolerability and recommended phase 2 dose of B in combination with CP. We will also estimate ORR, progression free and overall survival. DCE-MRI at baseline and end of cycle 1 will be explored as a potential pharmacodynamics biomarker in up to 10 patients. Due to theoretical concern for prothrombotic effects of B, an optional but encouraged prothrombotic evaluation will be performed on all consenting patients, consisting of baseline and end of study Doppler ultrasound, and blood collection for evaluation of D-Dimer and tissue-factor microparticles. Results: As of November 2011, Cohort 1 is complete with 3 patients (67% female, 100% white), median age of 59 (range 52-65y) at B dose 0.3 mg/kg. Safety data for cohort 1 is as follows: grade 3 thrombocytopenia attributed to CP was reported in one patient resulting in dosing interruption. No DLTs or SAEs have been reported. Currently 2 patients are evaluable for response, with both (100%) reporting partial responses. Conclusions: To date, the first of 3 planned dose escalations has been well tolerated, with no unexpected safety events. Response rates reported to date are encouraging, although conclusions are limited due to the small number. Dose escalation is ongoing and results will be updated.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1744. doi:1538-7445.AM2012-1744