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TRC105 is a chimeric IgG1 anti\u2010CD105\u00a0monoclonal antibody that inhibits angiogenesis and tumor growth by endothelial cell growth inhibition, ADCC and apoptosis, and complements VEGF inhibitors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim of this phase II study was to evaluate the efficacy of anti\u2010endoglin therapy with TRC105\u00a0in patients with advanced HCC, post\u2010sorafenib.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with HCC and compensated liver function (Childs\u2010Pugh A\/B7), ECOG 0\/1, were enrolled to a single\u2010arm, phase II study of TRC105 15\u2009mg\/kg IV every two weeks. Patients must have progressed on or been intolerant of prior sorafenib. A Simon optimal two\u2010stage design was employed with a 50% four\u2010month PFS target for progression to the second stage. Correlative biomarkers evaluated included DCE\u2010MRI as well as plasma levels of angiogenic biomarkers and soluble CD105.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total accrual of 27 patients was planned. However, because of lack of efficacy and in accordance with the Simon two\u2010stage design, 11 patients were enrolled. There were no grade 3\/4 treatment\u2010related toxicities. Most frequent toxicities were headache (G2; <jats:italic>N<\/jats:italic> \u2009=\u20093) and epistaxis (G1; <jats:italic>N<\/jats:italic> \u2009=\u20094). One patient had a confirmed partial response by standard RECIST criteria and biologic response on DCE\u2010MRI but the four\u2010month PFS was insufficient to proceed to the second stage of the study.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> TRC105 was well tolerated in this HCC population following sorafenib. Although there was evidence of clinical activity, this did not meet prespecified criteria to proceed to the second stage. TRC105 development in HCC continues as combination therapy with sorafenib.<\/jats:p><\/jats:sec>","DOI":"10.1177\/2050640615583587","type":"journal-article","created":{"date-parts":[[2015,4,29]],"date-time":"2015-04-29T01:22:30Z","timestamp":1430270550000},"page":"453-461","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":39,"title":["A phase II study of TRC105\u00a0in patients with hepatocellular carcinoma who have progressed on sorafenib"],"prefix":"10.1002","volume":"3","author":[{"given":"AG","family":"Duffy","sequence":"first","affiliation":[{"name":"Gastrointestinal Malignancies Section Thoracic-GI Oncology Branch Center for Cancer Research National Cancer Institute USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SV","family":"Ulahannan","sequence":"additional","affiliation":[{"name":"Gastrointestinal Malignancies Section Thoracic-GI Oncology Branch Center for Cancer Research National Cancer 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