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Title: Efficacy and safety results of ABT-414 in combination with radiation and temozolomide in newly diagnosed glioblastoma
Austin Authors: Reardon, David A;Lassman, Andrew B;van den Bent, Martin;Kumthekar, Priya;Merrell, Ryan;Scott, Andrew M ;Fichtel, Lisa;Sulman, Erik P;Gomez, Erica;Fischer, JuDee;Lee, Ho-Jin;Munasinghe, Wijith;Xiong, Hao;Mandich, Helen;Roberts-Rapp, Lisa;Ansell, Peter;Holen, Kyle D;Gan, Hui K 
Affiliation: Department of Medical Oncology, Austin Health, Heidelberg, Victoria, Australia
Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
Department of Neurology & Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York
Neuro-Oncology Unit, Erasmus MC Cancer Center, Rotterdam, the Netherlands
Department of Neurology, Northwestern University, Chicago, Illinois
Department of Neurology, NorthShore University HealthSystem, Evanston, Illinois
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
South Texas Accelerated Research Therapeutics (START), San Antonio, Texas
Department of Radiation Oncology, The University of Texas M.D.Anderson Cancer Center, Houston, Texas
AbbVie Inc., North Chicago, Illinois
Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
Issue Date: 1-Jul-2017
Date: 2016-12-30
Publication information: Neuro-Oncology 2016; 19(7): 965-975
Abstract: BACKGROUND: The purpose of this study was to determine the maximum tolerated dose (MTD), recommended phase II dose (RPTD), safety, and pharmacokinetics of ABT-414 plus radiation and temozolomide in newly diagnosed glioblastoma. ABT-414 is a first-in-class, tumor-specific antibody-drug conjugate that preferentially targets tumors expressing overactive epidermal growth factor receptor (EGFR). METHODS: In this multicenter phase I study, patients received 0.5-3.2 mg/kg ABT-414 every 2 weeks by intravenous infusion. EGFR alterations, O6-methylguanine-DNA methyltransferase (MGMT) promoter hypermethylation, and isocitrate dehydrogenase (IDH1) gene mutations were assessed in patient tumors. Distinct prognostic classes were assigned to patients based on a Molecular Classification Predictor model. RESULTS: As of January 7, 2016, forty-five patients were enrolled to receive ABT-414 plus radiation and temozolomide. The most common treatment emergent adverse events were ocular: blurred vision, dry eye, keratitis, photophobia, and eye pain. Ocular toxicity at any grade occurred in 40 patients and at grades 3/4 in 12 patients. RPTD and MTD were set at 2 mg/kg and 2.4 mg/kg, respectively. Among 38 patients with pretreatment tumor tested centrally, 39% harbored EGFR amplification, of which 73% had EGFRvIII mutation. Among patients with available tumor tissue (n = 30), 30% showed MGMT promoter methylation and none had IDH1 mutations. ABT-414 demonstrated an approximately dose proportional pharmacokinetic profile. The median duration of progression-free survival was 6.1 months; median overall survival has not been reached. CONCLUSION: ABT-414 plus chemoradiation demonstrated an acceptable safety and pharmacokinetic profile in newly diagnosed glioblastoma. Randomized studies are ongoing to determine efficacy in newly diagnosed (NCT02573324) and recurrent glioblastoma (NCT02343406).
DOI: 10.1093/neuonc/now257
Journal: Neuro-Oncology
PubMed URL:
Type: Journal Article
Subjects: ABT-414
Antibody-drug conjugate
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