Phase 1b study of gemcitabine, nab-paclitaxel, and ficlatuzumab in patients with advanced pancreatic cancer.

TPS4152Background: Nearly 80% of patients diagnosed with pancreatic ductal adenocarcinoma(PDAC) present with advanced, unresectable disease at the time of diagnosis, and as a result only about 4% will live 5 years after diagnosis. Paired-related homeodomain transcription factor 1 (Prrx1) isoforms – Prrx1a and 1b - are involved in pancreatic development, pancreatitis, and carcinogenesis. Prrx1a stimulates metastatic outgrowth and mesenchymal-epithelial transition(MET). Prrx1b promotes invasion and epithelial-mesenchymal transition (EMT). HGF is a novel transcriptional target of Prrx1b. Ficlatuzumab is a potent and selective recombinant humanized hepatocyte growth factor (HGF) inhibitory immunoglobulin G subclass 1 monoclonal antibody. It neutralizes HGF/c-Met binding and HGF-induced c-Met phosphorylation thereby inhibiting the c-Met pathway which has been associated with progression from primary to metastatic disease. In preclinical pancreatic adenocarcinoma models, inhibition of Prrx1b-HGF signaling using...