Effect of AMG 479 on anti-tumor effects of gemcitabine and erlotinib against pancreatic carcinoma xenograft models

• DOI: 10.1200/jco.2008.26.15_suppl.4617
• Publication Date: 2017-02-24T02:33:44Z
• Authors: P. J. Beltran; P. Mitchell; G. Moody; Y. Chung; E. Cajulis; B. Belmontes; R. Radinsky; F. Calzone
• Keywords: Cabozantinib

4617 Background: Binding of IGF-1 or IGF-2 to the type I insulin-like growth factor receptor (IGF-1R) activates intracellular signals important in and survival pancreatic tumors. AMG 479 is a fully human monoclonal antibody against IGF-1R currently phase II clinical trials. exerts its anti-tumor activity by blocking ligand binding inducing downregulation vivo. Methods: Insulin Receptor (IR) levels were determined using FACS analysis Meso Scale Detection (MSD). Level AKT phosphorylation measured MSD. Animal experiments performed injecting 5 million MiaPaCa BxPC-3 cells subcutaneously into female athymic nude mice. Treatment began when xenografts (n=10/group) approximately 200 mm3 continued for length experiment. gemcitabine dosed 2x/week intraperitoneally. Erlotinib was orally every day. Repeated measures ANOVA used compare efficacy treatment groups. Results: The ratios IR 60:1 1.5:1 cell lines, respectively. In vitro, blocked induced activation both lines. vivo, lines but could only block line. Dose- dependent tumor inhibition observed carcinoma xenograft models. Maximal (70%) achieved with 300 μg/dose, schedule. Analysis following revealed significant down- regulation expression (>60%). Since driven have been shown convey resistance traditional therapies, we tested ability enhance erlotinib Both significantly more effective combination 479. Furthermore, triple optimal doses 479, resulted stasis regression. Conclusions: These results demonstrate that blockade inhibits signaling enhances vivo effects approved therapies carcinoma. Author Disclosure Employment Leadership Consultant Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen