Abstract A161: Cardiovascular safety profile of BIND-014 (docetaxel nanoparticles for injectable suspension) evaluated in phase 1 and 2 studies
Authors: Summa Jason , Kung Jean , Adams Lisa K. , Zale Stephen E. , Youssoufian Hagop 
Published: May 2016

Abstract
Background: BIND-014 is a novel, prostate-specific membrane antigen (PSMA) targeted Accurin™ (polymeric nanoparticle) that contains docetaxel. PSMA is expressed on prostate cancer cells and on vasculature of many solid tumors types. In a phase 1 study in patients with solid tumors and two phase 2 studies, one study in patients with metastatic castration-resistant prostate cancer (mCRPC) and one study in non-small cell lung cancer (NSCLC), BIND-014 was generally well-tolerated and displayed anti-tumor activity across a range of tumor types. Because docetaxel-induced microtubule stabilization has the potential to cause contractile dysfunction in cardiac hypertrophy, the effects of BIND-014 on the cardiovascular system (CV) were examined.
Material and Methods: Data from phase 1 and 2 studies were analyzed to determine the cardiovascular effects of BIND-014 administered by a 60-minute intravenous infusion at doses ranging from 3.5-75 mg/m2 on Day 1 of a 21-day cycle (Q3W). Electrocardiogram (ECG) measurements pre- and post-infusion were taken to determine the PR interval, QTc interval, RR interval and QRS complex. In addition, vital signs were collected for heart rate, respiratory rate, and pulse ox (phase 2 only) prior to infusion. Additional treatment-related adverse events (AEs) classified as cardiac disorders were collected throughout the patients' treatment.
Results: For all 110 patients tested, the ECG data collected (PR, QTc, and QRS) remained in normal or clinically insignificant abnormal limits. Vitals signs for heart rate, respiratory rate, and pulse ox were also within normal or clinically insignificant abnormal limits. Seven patients experienced drug-related AEs ranging from grade (gr) 1-3; all 7 patients were dosed at 60 mg/m2. These included sinus tachycardia (3 pts, gr 1-2), angina pectoris (2 pts, gr 1&3), atrial fibrillation (1 pt, gr 1), bundle branch block right (1 pt, gr 1), supraventricular extrasystoles (1 pt, gr 1), supraventricular tachycardia (1 pt, gr 1), and tachycardia (1 pt, gr 1). Patients dosed below 60 mg/m2 did not experience any drug-related cardiovascular AEs.
Conclusions: BIND-014 administered on a Q3W schedule in the phase 1 and 2 studies appeared well-tolerated at all dose levels studied. For all ECG and pulmonary evaluations, there were no indications of clinically significant cardiac abnormalities, and the incidence and severity of AEs was low. The results provide a basis for concluding that BIND-014 is a safe antitumor agent without the cardiovascular effects typically associated docetaxel.
Citation Format: Jason Summa, Jean Kung, Lisa K. Adams, Stephen E. Zale, Hagop Youssoufian. Cardiovascular safety profile of BIND-014 (docetaxel nanoparticles for injectable suspension) evaluated in phase 1 and 2 studies. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A161.