OFP-04-006 Development of a rabbit monoclonal antibody for determining hENT1 status and predicting response to gemcitabine in pancreatic ductal adenocarcinoma M. Raponi * , J. Isaacson, J. Ranger-Moore, J. Clements, B. Richardson, S. Ormanns, K. Winter, A. Allen, R. Andersson, V. Heinemann, A. P. Dicker * Clovis Oncology, San Francisco, CA, USA Objective: Human equilibrative nucleoside transporter 1 (hENT1) is the primary membrane channel through which gemcitabine (Gem) enters pancreatic tumor cells, and patients whose tumors have low expression of hENT1 may derive little benefit from Gem therapy. Method: An analytically validated rabbit monoclonal antibody immunohistochemistry (IHC) in vitro diagnostic (IVD) for assessing the degree of hENT1 expression in pancreatic adenocarcinoma using an automated IHC platform has been developed. Results: Using primary tumor samples (n=201) from a randomized controlled clinical adjuvant trial (RTOG 97-04), we developed and verified a hENT1 scoring methodology and cut-off for identifying patients least likely to benefit from Gem (hENT1-low). The distribution of hENT1 expression was similar between these samples and an independent set of 130 pancreatic adenocarcinoma specimens from the AIO-PK0104 study of which 77 were confirmed metastatic biopsies. Overall, using this cut-off, approximately two thirds of pancreatic tumors displayed low-hENT1 expression across the different data sets. Conclusion: A robust hENT1 IHC IVD has been developed using a rabbit monoclonal antibody and identifies two thirds of primary and metastatic PDAC cases as having low expression of hENT1.