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Neuro Oncol. 2019 Jan 1;21(1):106-114. doi: 10.1093/neuonc/noy091.

Safety and efficacy of depatuxizumab mafodotin + temozolomide in patients with EGFR-amplified, recurrent glioblastoma: results from an international phase I multicenter trial.

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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 and Olivia Newton-John Cancer Research Institute, Melbourne, Victoria, Australia.
Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Northwestern University, Chicago, Illinois, USA.
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.
Henry Ford Health System, Detroit, Michigan, USA.
University of Alabama at Birmingham, Birmingham, Alabama, 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.
Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia.
AbbVie Inc., North Chicago, Illinois, USA.
NorthShore University Health System, Evanston, Illinois, USA.



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).

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