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Cancer Chemother Pharmacol. 2017 Dec;80(6):1209-1217. doi: 10.1007/s00280-017-3451-1. Epub 2017 Oct 26.

Efficacy of depatuxizumab mafodotin (ABT-414) monotherapy in patients with EGFR-amplified, recurrent glioblastoma: results from a multi-center, international study.

Author information

1
Brain Tumor Center, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, the Netherlands. m.vandenbent@erasmusmc.nl.
2
School of Cancer Medicine, La Trobe University, Melbourne, VIC, Australia.
3
Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.
4
Department of Neurology and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA.
5
Northwestern University, Chicago, IL, USA.
6
NorthShore University Health System, Evanston, IL, USA.
7
Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
8
Department of Medical Oncology, School of Medicine, University of Queensland, Royal Brisbane and Women's Hospital, Brisbane, Australia.
9
Henry Ford Health System, Detroit, MI, USA.
10
University of Alabama at Birmingham, Birmingham, AL, USA.
11
South Texas Accelerated Research Therapeutics (START), San Antonio, TX, USA.
12
The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
13
NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia.
14
Medical Oncology, Royal North Shore Hospital, Sydney, NSW, Australia.
15
AbbVie Inc., North Chicago, IL, USA.
16
Dana-Farber Cancer Institute, Boston, MA, USA.

Abstract

PURPOSE:

Patients with recurrent glioblastoma (rGBM) have a poor prognosis. Epidermal growth factor receptor (EGFR) gene amplification is present in ~ 50% of glioblastomas (GBMs). Depatuxizumab mafodotin (depatux-m), formerly ABT-414, is an antibody-drug conjugate that preferentially binds cells with EGFR amplification, is internalized and releases a potent antimicrotubule agent, monomethyl auristatin F (MMAF). Here we report the safety, pharmacokinetics, and efficacy of depatux-m monotherapy at the recommended Phase 2 dose (RPTD) in patients with EGFR-amplified, rGBM.

METHODS:

M12-356 (NCT01800695) is an open-label study with three escalation and expansion cohorts. Sixty-six patients with EGFR-amplified, rGBM were treated with depatux-m monotherapy at 1.25 mg/kg intravenously every 2 weeks. Adults with measurable rGBM, who were bevacizumab-naïve, with EGFR amplification were eligible.

RESULTS:

Among 66 patients, median age was 58 years (range 35-80). All patients were previously treated with radiotherapy/temozolomide. The most common adverse events (AEs) were eye related (91%), including blurred vision (65%), dry eye (29%), keratitis, and photophobia (27% each). Grade 3/4 AEs occurred in 42% of all patients, and ocular Grade 3/4 AEs occurred in 33% of patients overall. One patient (2%) had a Grade 4 ocular AE. Ocular AEs were manageable and usually resolved once treatment with depatux-m ceased. The objective response rate was 6.8%, the 6-month progression-free survival rate was 28.8%, and the 6-month overall survival rate was 72.5%.

CONCLUSION:

Depatux-m monotherapy displayed frequent but mostly Grade 1/2 ocular toxicities. A PFS6 of 28.8% was observed in this rGBM population, warranting further study.

KEYWORDS:

ABT-414; Antibody–drug conjugate; Depatuxizumab mafodotin; EGFR; Recurrent glioblastoma

PMID:
29075855
PMCID:
PMC5686264
DOI:
10.1007/s00280-017-3451-1
[Indexed for MEDLINE]
Free PMC Article

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