A phase I study of TRC105 anti‐endoglin (CD105) antibody in metastatic castration‐resistant prostate cancer. (8th June 2015)

• Record Type: Journal Article
• Authors: Karzai, Fatima H.; Apolo, Andrea B.; Cao, Liang; Madan, Ravi A.; Adelberg, David E.; Parnes, Howard; McLeod, David G.; Harold, Nancy; Peer, Cody; Yu, Yunkai; Tomita, Yusuke; Lee, Min‐Jung; Lee, Sunmin; Trepel, Jane B.; Gulley, James L.; Figg, William D.; Dahut, William L.
• Is Part Of: BJU international. Volume 116:Number 4(2015:Oct.)
• Page Start: 546
• Page End: 555
• Publication Date: 2015-06-08
• Subjects: Genitourinary organs -- Diseases -- Periodicals; Genitourinary organs -- Surgery -- Periodicals; Urology -- Periodicals; 616.6
• DOI: 10.1111/bju.12986
• Languages: English
• ISSNs: 1464-4096

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bju12986-sec-0001" sec-type="section"> <title>Objective</title> <p>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).</p> </sec> <sec id="bju12986-sec-0002" sec-type="section"> <title>Patients and Methods</title> <p>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.</p> </sec> <sec id="bju12986-sec-0003" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="bju12986-sec-0004" sec-type="section"> <title>Conclusion</title> <p>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.</p> </sec> </abstract>