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Title: Safety and efficacy of depatuxizumab mafodotin + temozolomide in patients with EGFR-amplified, recurrent glioblastoma: results from an international phase I multicenter trial.
Authors: Lassman, Andrew B;van den Bent, Martin J;Gan, Hui K;Reardon, David A;Kumthekar, Priya;Butowski, Nicholas;Lwin, Zarnie;Mikkelsen, Tom;Nabors, Louis B;Papadopoulos, Kyriakos P;Penas-Prado, Marta;Simes, John;Wheeler, Helen;Walbert, Tobias;Scott, Andrew M;Gomez, Erica;Lee, Ho-Jin;Roberts-Rapp, Lisa;Xiong, Hao;Ansell, Peter J;Bain, Earle;Holen, Kyle D;Maag, David;Merrell, Ryan
Affiliation: Department of Neurology and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA
Erasmus MC Cancer Institute, Rotterdam, Netherlands
School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
Austin Health, Heidelberg, Victoria, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
Northwestern University, Chicago, Illinois, USA
South Texas Accelerated Research Therapeutics (START), San Antonio, Texas, USA
The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia
Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA
Department of Medical Oncology, University of Queensland School of Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
University of Alabama at Birmingham, Birmingham, Alabama, USA
Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia
Henry Ford Health System, Detroit, Michigan, USA
AbbVie Inc., North Chicago, Illinois, USA
NorthShore University Health System, Evanston, Illinois, USA
Issue Date: 2018
EDate: 2018-07-05
Citation: Neuro-oncology 2018; online first: 5 July
Abstract: Patients with glioblastoma (GBM) have a dismal prognosis. Nearly all will relapse with no clear standard of care for recurrent disease (rGBM). Approximately 50% of patients have tumors harboring epidermal growth factor receptor (EGFR) amplification. The antibody-drug conjugate depatuxizumab mafodotin (depatux-m) binds cells with EGFR amplification, is internalized, and releases a microtubule toxin, killing the cell. Here we report efficacy, safety and pharmacokinetics (PK) of depatux-m + temozolomide (TMZ) in patients with EGFR-amplified rGBM. M12-356 (NCT01800695) was an open-label study encompassing patients with newly diagnosed or rGBM across 3 treatment arms. Results are reported for adults with EGFR-amplified, measurable rGBM who received depatux-m (0.5-1.5 mg/kg) on days 1 and 15, and TMZ (150-200 mg/m2) on days 1-5 in a 28-day cycle. Patients were bevacizumab and nitrosourea naïve. There were 60 patients, median age 56 years (range, 20-79). Fifty-nine patients previously received TMZ. Common adverse events (AEs) were blurred vision (63%), fatigue (38%), and photophobia (35%). Grades 3/4 AEs were split between ocular and non-ocular AEs, occurring in 22% of patients each. Systemic PK exposure of depatux-m was dose proportional. The objective response rate was 14.3%, the 6-month progression-free survival rate was 25.2%, and the 6-month overall survival rate was 69.1%. Depatux-m + TMZ displayed an AE profile similar to what was described previously. Antitumor activity in this TMZ-refractory population was encouraging. Continued study of depatux-m in patients with EGFR-amplified, newly diagnosed, or recurrent GBM is ongoing in 2 global, randomized trials (NCT02573324, NCT02343406).
DOI: 10.1093/neuonc/noy091
ORCID: 0000-0002-6656-295X
PubMed URL: 29982805
Type: Journal Article
Appears in Collections:Journal articles

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