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

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    Author
    van den Bent, M; Gan, HK; Lassman, AB; Kumthekar, P; Merrell, R; Butowski, N; Lwin, Z; Mikkelsen, T; Nabors, LB; Papadopoulos, KP; ...
    Date
    2017-12-01
    Source Title
    Cancer Chemotherapy and Pharmacology
    Publisher
    SPRINGER
    University of Melbourne Author/s
    Scott, Andrew; Gan, Hui
    Affiliation
    Medicine and Radiology
    Metadata
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    Document Type
    Journal Article
    Citations
    van den Bent, M., Gan, H. K., Lassman, A. B., Kumthekar, P., Merrell, R., Butowski, N., Lwin, Z., Mikkelsen, T., Nabors, L. B., Papadopoulos, K. P., Penas-Prado, M., Simes, J., Wheeler, H., Walbert, T., Scott, A. M., Gomez, E., Lee, H. -J., Roberts-Rapp, L., Xiong, H. ,... Reardon, D. A. (2017). Efficacy of depatuxizumab mafodotin (ABT-414) monotherapy in patients with EGFR-amplified, recurrent glioblastoma: results from a multi-center, international study. CANCER CHEMOTHERAPY AND PHARMACOLOGY, 80 (6), pp.1209-1217. https://doi.org/10.1007/s00280-017-3451-1.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/257413
    DOI
    10.1007/s00280-017-3451-1
    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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