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dc.contributor.authorvan den Bent, M
dc.contributor.authorGan, HK
dc.contributor.authorLassman, AB
dc.contributor.authorKumthekar, P
dc.contributor.authorMerrell, R
dc.contributor.authorButowski, N
dc.contributor.authorLwin, Z
dc.contributor.authorMikkelsen, T
dc.contributor.authorNabors, LB
dc.contributor.authorPapadopoulos, KP
dc.contributor.authorPenas-Prado, M
dc.contributor.authorSimes, J
dc.contributor.authorWheeler, H
dc.contributor.authorWalbert, T
dc.contributor.authorScott, AM
dc.contributor.authorGomez, E
dc.contributor.authorLee, H-J
dc.contributor.authorRoberts-Rapp, L
dc.contributor.authorXiong, H
dc.contributor.authorBain, E
dc.contributor.authorAnsell, PJ
dc.contributor.authorHolen, KD
dc.contributor.authorMaag, D
dc.contributor.authorReardon, DA
dc.date.accessioned2020-12-21T03:55:39Z
dc.date.available2020-12-21T03:55:39Z
dc.date.issued2017-12-01
dc.identifierpii: 10.1007/s00280-017-3451-1
dc.identifier.citationvan 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.
dc.identifier.issn0344-5704
dc.identifier.urihttp://hdl.handle.net/11343/257413
dc.description.abstractPURPOSE: 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.
dc.languageEnglish
dc.publisherSPRINGER
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleEfficacy of depatuxizumab mafodotin (ABT-414) monotherapy in patients with EGFR-amplified, recurrent glioblastoma: results from a multi-center, international study
dc.typeJournal Article
dc.identifier.doi10.1007/s00280-017-3451-1
melbourne.affiliation.departmentMedicine (Austin & Northern Health)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleCancer Chemotherapy and Pharmacology
melbourne.source.volume80
melbourne.source.issue6
melbourne.source.pages1209-1217
dc.rights.licenseCC BY
melbourne.elementsid1271163
melbourne.contributor.authorScott, Andrew
melbourne.contributor.authorGan, Hui
dc.identifier.eissn1432-0843
melbourne.accessrightsOpen Access


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