OBJECTIVE: TRC105 is a chimeric IgG1 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 intravenous TRC105 until unacceptable toxicity or disease progression, up to a predetermined dose level using a standard 3+3 phase I design.
RESULTS: Twenty patients were treated and the top dose level studied of 20 mg/kg every two weeks was the maximum tolerated dose. Common adverse effects included infusion-related reaction (90%), low grade headache (67%), anemia (48%), epistaxis (43%), and fever (43%). Ten patients had stable disease on study and eight patients had PSA declines. 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. There was a significant induction of plasma VEGF associated with CD105 reduction, suggesting anti-angiogenic activity of TRC105. An exploratory analysis revealed a tentative correlation between the reduction of CD105 and a decrease in PSA velocity, suggestive of potential activity of TRC105 in the CRPC patients. The data from this exploratory analysis suggests rising VEGF is a possible compensatory mechanism for TRC105 induced anti-angiogenic activity.
Written by:
Karzai FH, Apolo AB, Cao L, Madan RA, Adelberg DE, Parnes H, McLeod DG, Harold N, Peer C, Yu Y, Tomita Y, Lee MJ, Lee S, Trepel JB, Gulley JL, Figg WD, Dahut WL. Are you the author?
Reference: BJU Int. 2014 Nov 19. Epub ahead of print.
doi: 10.1111/bju.12986
PubMed Abstract
PMID: 25407442
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