Abstract B17: PDL192, a humanized antibody to TweakR exhibits potent antitumor activity in pancreatic cancer models

Abstract

Abstract Approximately 42,000 new cases of pancreatic cancer were diagnosed in the United States in 2009, and the 5-year survival rate for this disease is exceedingly low (approximately 5%). Given the lack of therapeutic success with current standards of care, new therapies are clearly needed to treat this disease. We have generated PDL192, a humanized IgG1 antibody to TweakR (Fn14, TNFRSF12A, CD266), a cell surface protein and member of the TNF receptor superfamily. PDL192 has been shown to exhibit antitumor activity in xenograft models on a range of solid tumor types via both direct tumor cell growth inhibition and by antibody-dependent cellular cytotoxicity. In this study, we explored the activity of PDL192 in pancreatic cancer models. Approximately 60% of primary pancreatic cancers express TweakR protein at high levels, as determined by immunohistochemistry. PDL192 exhibited potent anti-tumor activity in two cell line xenograft models, Panc1 and MiaPaCa2. PDL192 also exhibited significant anti-tumor activity against 3 of 6 primary tumor xenograft models derived from pancreatic patients. PDL192 was also tested in combination with gemcitabine, the most common treatment for pancreatic cancer patients. In the Panc1 and MiaPaCa2 xenograft models, the combination of PDL192 and gemcitabine exhibited more potent activity than either agent alone. In three of five primary tumor xenograft models tested, combining PDL192 and gemcitabine also resulted in greater anti-tumor activity than either agent alone. In one of the primary tumor models, where neither PDL192 nor gemcitabine alone exhibited significant anti-tumor activity, the combination completely inhibited tumor growth. The activity of PDL192 in multiple pancreatic xenograft models using both cell lines and primary tumors is supportive of the use of PDL192 for the treatment of pancreatic cancer. PDL192 is currently being evaluated in a phase1 safety study in patients with solid tumors. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B17.