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https://hdl.handle.net/2440/106369
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Type: | Journal article |
Title: | A phase I study of olaratumab, an anti-platelet-derived growth factor receptor alpha (PDGFRα) monoclonal antibody, in patients with advanced solid tumors |
Author: | Chiorean, E. Sweeney, C. Youssoufian, H. Qin, A. Dontabhaktuni, A. Loizos, N. Nippgen, J. Amato, R. |
Citation: | Cancer Chemotherapy and Pharmacology, 2014; 73(3):595-604 |
Publisher: | Springer |
Issue Date: | 2014 |
ISSN: | 0344-5704 1432-0843 |
Statement of Responsibility: | E. Gabriela Chiorean, Christopher Sweeney, Hagop Youssoufian, Amy Qin, Aruna Dontabhaktuni, Nick Loizos, Johannes Nippgen, Robert Amato |
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), recommended 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 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 concentrations (C min) for 16 mg/kg weekly and 20 mg/kg biweekly were higher than 155 μg/mL, and the concentration 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 olaratumab as monotherapy and in combination are ongoing in several tumor types. |
Keywords: | Olaratumab; IMC-3G3; platelet-derived growth factor receptor; solid tumors; phase I |
Rights: | © Springer-Verlag Berlin Heidelberg 2014 |
DOI: | 10.1007/s00280-014-2389-9 |
Published version: | http://dx.doi.org/10.1007/s00280-014-2389-9 |
Appears in Collections: | Aurora harvest 3 Pharmacology publications |
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