A phase i study of TRC105 anti-endoglin (CD105) antibody in metastatic castration-resistant prostate cancer

Fatima H. Karzai, Andrea B. Apolo, Liang Cao, Ravi A. Madan, David E. Adelberg, Howard Parnes, David G. McLeod, Nancy Harold, Cody Peer, Yunkai Yu, Yusuke Tomita, Min Jung Lee, Sunmin Lee, Jane B. Trepel, James L. Gulley, William D. Figg, William L. Dahut*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Objective TRC105 is a chimeric immunoglobulin G1 monoclonal antibody that binds endoglin (CD105). This phase I open-label study evaluated the safety, pharmacokinetics and pharmacodynamics of TRC105 in patients with metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods Patients with mCRPC received escalating doses of i.v. TRC105 until unacceptable toxicity or disease progression, up to a predetermined dose level, using a standard 3 + 3 phase I design. Results A total of 20 patients were treated. The top dose level studied, 20 mg/kg every 2 weeks, was the maximum tolerated dose. Common adverse effects included infusion-related reaction (90%), low grade headache (67%), anaemia (48%), epistaxis (43%) and fever (43%). Ten patients had stable disease on study and eight patients had declines in prostate specific antigen (PSA). Significant plasma CD105 reduction was observed at the higher dose levels. In an exploratory analysis, vascular endothelial growth factor (VEGF) was increased after treatment with TRC105 and VEGF levels were associated with CD105 reduction. Conclusion TRC105 was tolerated at 20 mg/kg every other week with a safety profile distinct from that of VEGF inhibitors. A significant induction of plasma VEGF was associated with CD105 reduction, suggesting anti-angiogenic activity of TRC105. An exploratory analysis showed a tentative correlation between the reduction of CD105 and a decrease in PSA velocity, suggestive of potential activity of TRC105 in the patients with mCRPC. The data from this exploratory analysis suggest that rising VEGF level is a possible compensatory mechanism for TRC105-induced anti-angiogenic activity.

Original languageEnglish
Pages (from-to)546-555
Number of pages10
JournalBJU International
Volume116
Issue number4
DOIs
StatePublished - 1 Oct 2015
Externally publishedYes

Keywords

  • TRC105
  • angiogenesis inhibitors
  • anti CD105
  • endogolin
  • metastatic
  • prostate cancer

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