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Title: Safety, pharmacokinetics, and antitumor response of depatuxizumab mafodotin as monotherapy or in combination with temozolomide in patients with glioblastoma.
Austin Authors: Gan, Hui K ;Reardon, David A;Lassman, Andrew B;Merrell, Ryan;van den Bent, Martin;Butowski, Nicholas;Lwin, Zarnie;Wheeler, Helen;Fichtel, Lisa;Scott, Andrew M ;Gomez, Erica J;Fischer, JuDee;Mandich, Helen;Xiong, Hao;Lee, Ho-Jin;Munasinghe, Wijith P;Roberts-Rapp, Lisa A;Ansell, Peter J;Holen, Kyle D;Kumthekar, Priya
Affiliation: Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
Department of Medical Oncology, Austin Health, Heidelberg, Victoria, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University School of Cancer Medicine, Melbourne, Victoria, Australia
Department of Neurology & Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York, USA
Department of Neurology, NorthShore University HealthSystem, Evanston, Illinois, USA
Neuro-Oncology Unit, Erasmus MC Cancer Center, Rotterdam, the Netherlands
Department of Neurological Surgery, University of California, San Francisco, California, USA
Department of Medical Oncology, University of Queensland School of Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia
South Texas Accelerated Research Therapeutics, San Antonio, Texas, USA
AbbVie Inc., North Chicago, Illinois, USA
Department of Neurology, Northwestern University, Chicago, Illinois, USA
Issue Date: 18-May-2018
Publication information: Neuro-oncology 2018; 20(6): 838-847
Abstract: We recently reported an acceptable safety and pharmacokinetic profile of depatuxizumab mafodotin (depatux-m), formerly called ABT-414, plus radiation and temozolomide in newly diagnosed glioblastoma (arm A). The purpose of this study was to evaluate the safety and pharmacokinetics of depatux-m, either in combination with temozolomide in newly diagnosed or recurrent glioblastoma (arm B) or as monotherapy in recurrent glioblastoma (arm C). In this multicenter phase I dose escalation study, patients received depatux-m (0.5-1.5 mg/kg in arm B, 1.25 mg/kg in arm C) every 2 weeks by intravenous infusion. Maximum tolerated dose (MTD), recommended phase II dose (RP2D), and preliminary efficacy were also determined. Thirty-eight patients were enrolled as of March 1, 2016. The most frequent toxicities were ocular, occurring in 35/38 (92%) patients. Keratitis was the most common grade 3 adverse event observed in 6/38 (16%) patients; thrombocytopenia was the most common grade 4 event seen in 5/38 (13%) patients. The MTD was set at 1.5 mg/kg in arm B and was not reached in arm C. RP2D was declared as 1.25 mg/kg for both arms. Depatux-m demonstrated a linear pharmacokinetic profile. In recurrent glioblastoma patients, the progression-free survival (PFS) rate at 6 months was 30.8% and the median overall survival was 10.7 months. Best Response Assessment in Neuro-Oncology responses were 1 complete and 2 partial responses. Depatux-m alone or in combination with temozolomide demonstrated an acceptable safety and pharmacokinetic profile in glioblastoma. Further studies are currently under way to evaluate its efficacy in newly diagnosed (NCT02573324) and recurrent glioblastoma (NCT02343406).
DOI: 10.1093/neuonc/nox202
ORCID: 0000-0002-6656-295X
Journal: Neuro-oncology
PubMed URL: 29077941
Type: Journal Article
Appears in Collections:Journal articles

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