1 3 Cancer Chemother Pharmacol (2014) 73:595–604 DOI 10.1007/s00280-014-2389-9 ORIGINAL ARTICLE A phase I study of olaratumab, an anti-platelet-derived growth factor receptor alpha (PDGFRα) monoclonal antibody, in patients with advanced solid tumors E. Gabriela Chiorean · Christopher Sweeney · Hagop Youssoufian · Amy Qin · Aruna Dontabhaktuni · Nick Loizos · Johannes Nippgen · Robert Amato Received: 18 December 2013 / Accepted: 13 January 2014 / Published online: 23 January 2014 © Springer-Verlag Berlin Heidelberg 2014 not identified with the doses studied. The most common olaratumab-related adverse events (AE) were fatigue and infusion reactions (10.5 % each). With the exception of 1 patient (20 mg/kg) experiencing two grade 3 drug-related AEs after the dose-limiting toxicity assessment period, all drug-related AEs were grade 1 or 2. The trough con- centrations (C min ) for 16 mg/kg weekly and 20 mg/kg biweekly were higher than 155 μg/mL, and the concen- tration found to be efficacious in preclinical xenograft models. Twelve patients (63.2 %) had a best response of stable disease [median duration of 3.9 months (95 % CI 2.3–8.7)]. Conclusions Olaratumab was well tolerated and showed preliminary antitumor activity. RP2Ds are 16 mg/kg weekly and 20 mg/kg biweekly. Phase II studies of olara- tumab as monotherapy and in combination are ongoing in several tumor types. Keywords Olaratumab · IMC-3G3 · Platelet-derived growth factor receptor · Solid tumors · Phase I Abstract Purpose The platelet-derived growth factor receptor (PDGFR) has an important role in tumorigenesis and tumor progression. Olaratumab (IMC-3G3) is a fully human monoclonal antibody that selectively binds human PDGFRα and blocks ligand binding. This phase I study assessed the safety, maximum tolerated dose (MTD), rec- ommended phase II dose (RP2D), pharmacokinetics, and preliminary antitumor activity of olaratumab in patients with advanced solid tumors. Methods Patients were enrolled into five dose-escalating cohorts of 3–6 patients each. Olaratumab was administered intravenously weekly at 4, 8, or 16 mg/kg (cohorts 1–3) or once every other week at 15 or 20 mg/kg (cohorts 4–5), with 4 weeks/cycle. Results Nineteen patients were treated in five cohorts. There were no dose-limiting toxicities; the MTD was Presented in part at the EORTC-NCI-AACR Annual Meeting; October 21–24, 2008; Geneva, Switzerland [abstract 511 and poster]. E. G. Chiorean (*) Fred Hutchinson Cancer Research Center, University of Washington, 825 Eastlake Ave East, G4830, Seattle, WA 98109, USA e-mail: gchiorea@uw.edu E. G. Chiorean Indiana University, 535 Barnhill Drive, Indianapolis, IN, USA C. Sweeney Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA H. Youssoufian · A. Qin · A. Dontabhaktuni · N. Loizos ImClone Systems LLC (a wholly owned subsidiary of Eli Lilly and Company), Bridgewater, NJ, USA Present Address: H. Youssoufian Progenics Pharmaceuticals, Tarrytown, NY, USA J. Nippgen ImClone Systems LLC (a wholly owned subsidiary of Eli Lilly and Company), Heidelberg, Germany Present Address: J. Nippgen Glycotope GmbH, Berlin, Germany R. Amato Memorial Hermann Cancer Center-Texas Medical Center, University of Texas Health Science Center at Houston, Houston, TX, USA