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We aimed to evaluate the safety profile, maximum tolerated dose (MTD), pharmacokinetics, and antitumor activity of MEDI-547, an antibody drug conjugate composed of the cytotoxic drug auristatin (toxin) linked to a human anti-EphA2 monoclonal antibody (1C1), in patients with solid tumors relapsed\/refractory to standard therapy.\n                    <jats:italic>Methods<\/jats:italic>\n                    In this phase 1, open-label study with planned dose-escalation and dose-expansion cohorts, patients received a 1-h intravenous infusion of MEDI-547 (0.08\u00a0mg\/kg) every 3\u00a0weeks.\n                    <jats:italic>Results<\/jats:italic>\n                    Six patients received 0.08\u00a0mg\/kg; all discontinued treatment. Dose escalation was not pursued. The study was stopped before cohort 2 enrollment due to treatment-related bleeding and coagulation events (hemorrhage-related,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20093; epistaxis,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20092). Therefore, lower doses were not explored and an MTD could not be selected. The most frequently reported treatment-related adverse events (AEs) were increased liver enzymes, decreased hemoglobin, decreased appetite, and epistaxis. Three patients (50%) experienced treatment-related serious AEs, including conjunctival hemorrhage, pain (led to study drug discontinuation), liver disorder, and hemorrhage. Best response included progressive disease (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20095; 83.3%) and stable disease (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091; 16.7%). Minimal or no dissociation of toxin from 1C1 conjugate occurred in the blood. Serum MEDI-547 concentrations decreased rapidly, ~70% by 3\u00a0days post-dose. No accumulation of MEDI-547 was observed at 0.08\u00a0mg\/kg upon administration of a second dose 3\u00a0weeks following dose 1.\n                    <jats:italic>Conclusions<\/jats:italic>\n                    The safety profile of MEDI-547 does not support further clinical\n            investigation in patients with advanced solid tumors.\n                  <\/jats:p>","DOI":"10.1007\/s10637-012-9801-2","type":"journal-article","created":{"date-parts":[[2012,2,27]],"date-time":"2012-02-27T00:25:25Z","timestamp":1330302325000},"page":"77-84","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["Phase 1, open-label study of MEDI-547 in patients with relapsed or refractory solid tumors"],"prefix":"10.1007","volume":"31","author":[{"given":"Christina M.","family":"Annunziata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise C.","family":"Kohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"LoRusso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole D.","family":"Houston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Coleman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Buzoianu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Robbie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Lechleider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,2,28]]},"reference":[{"key":"9801_CR1","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1016\/S0002-9440(10)63899-0","volume":"162","author":"J Walker-Daniels","year":"2003","unstructured":"Walker-Daniels J, Hess AR, Hendrix MJ, Kinch MS (2003) Differential regulation of EphA2 in normal and malignant cells. 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