Abstract 911: Prostate-specific membrane antigen (PSMA) expression as a potential patient selection marker in patients with refractory solid tumors administered BIND-014, a PSMA-targeted nanoparticle containing docetaxel

Abstract

Abstract Background: Prostate-specific membrane antigen (PSMA) is a transmembrane protein that is overexpressed in prostate adenocarcinomas and in non-prostatic tumor neovasculature. As a novel target for therapeutic approaches, the distribution pattern of PSMA in primary and metastatic tumors is of significant interest. In this study we addressed the cellular distribution and heterogeneity of PSMA expression in solid tumors from patients on a phase 1 study of BIND-014, a PSMA-targeted nanoparticle containing docetaxel.Methods: Paraffin-embedded sections of surgical specimens from 1 patient (pt) with prostate carcinoma and 4 pts with non-prostatic tumors (cervical, NSCLC, breast and hepatobiliary) were evaluated. Immunohistochemistry by platelet endothelial cell adhesion molecule (CD31) for the detection of endothelial cells and monoclonal mouse anti-human PSMA (Clone 3E6) for detection of PSMA were used to determine the cellular localization and staining intensity for each tumor type. Results: All pts evaluated experienced some clinical benefit from BIND-014 (including complete response, partial response or stable disease) which is targeted to PSMA. We demonstrated differences in staining intensity and localization of PSMA in neoplastic epithelium and neoplastic tissue-associated blood vessels. PSMA was detected in the epithelium of prostate tissue and in neoplastic tissue-associated vessels of cervical, anal, NSCLC, and hepatobiliary cancers. PSMA was not detected in benign tissue of any specimens evaluated. Conclusions: Our findings support the feasibility of developing this assay as a companion diagnostic to potentially select patients who may benefit from PSMA-directed targeted therapy. Ongoing Phase 2 studies with BIND-014 include further PSMA expression analysis. Citation Format: Susan Low, Daniel Von Hoff, Monica Mita, Howard Burris, Peter Eisenberg, Lowell Hart, Patricia LoRusso, Glen Weiss, Jasgit Sachdev, Alain Mita, Ramesh Ramanathan, Jeff Hrkach, Jason Summa, Gregory Berk. Prostate-specific membrane antigen (PSMA) expression as a potential patient selection marker in patients with refractory solid tumors administered BIND-014, a PSMA-targeted nanoparticle containing docetaxel. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 911. doi:10.1158/1538-7445.AM2014-911