Abstract 2048: Pharmacodynamic biomarker studies of TRC105 anti-endoglin (CD105) antibody revealed anti-angiogenic activity associated with CD105 depletion

Abstract

Abstract Introduction: CD105 is involved in normal vascular development. It is over expressed on the surface of proliferating vascular endothelial cells and is implicated in tumor angiogenesis. In hypoxic conditions, CD105 is upregulated through induction of hypoxia-inducible factor 1-α. TRC105 is a chimeric IgG1 antibody specific for CD105 and the agent for this phase I trial. Methods: 20 patients with metastatic prostate cancer were treated with TRC105 at six dose levels in a phase I trial. Blood samples were analyzed for CD105 antigen depletion, VEGF as a marker for systemic hypoxia, and PSA. Results: Maximum tolerated dose of 20 mg/kg every two weeks was reached. Significant plasma CD105 reduction was observed at high dose levels. The reduction of CD105 was associated with induction of plasma VEGF. Ten patients had stable disease, and the reduction of CD105 is associated with PSA stabilization. Conclusion: A significant induction of VEGF was associated with CD105 reduction at three high dose levels, suggesting the anti-angiogenic activity of TRC105. Exploratory analysis showed a tentative correlation between the reduced CD105 and a decreased PSA velocity, suggestive of potential antitumor activity of TRC105 in metastatic prostate cancer. Citation Format: Liang Cao, Fatima Karzai, Andrea Apolo, Ravi Madan, Yunkai Yu, James Gulley, William Figg, William Dahut. Pharmacodynamic biomarker studies of TRC105 anti-endoglin (CD105) antibody revealed anti-angiogenic activity associated with CD105 depletion. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2048.