Efficacy of Depatuxizumab Mafodotin (ABT-414) Monotherapy in Patients with EGFR-amplified, Recurrent Glioblastoma: Results from a Multi-center, International Study

Overview

Journal Cancer Chemother Pharmacol

Specialty Oncology

Date 2017 Oct 28

PMID 29075855

Citations 72

Authors

Martin van den Bent

Hui K Gan

Andrew B Lassman

Priya Kumthekar

Ryan Merrell

Nicholas Butowski

Zarnie Lwin

Tom Mikkelsen

Louis B Nabors

Kyriakos P Papadopoulos

Marta Penas-Prado

John Simes

Helen Wheeler

Tobias Walbert

Andrew M Scott

Erica Gomez

Ho-Jin Lee

Lisa Roberts-Rapp

Hao Xiong

Earle Bain

Peter J Ansell

Kyle D Holen

David Maag

David A Reardon

Affiliations

Soon will be listed here.

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.

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