Efficacy of depatuxizumab mafodotin (ABT-414) monotherapy in patients with EGFR-amplified, recurrent glioblastoma: results from a multi-center, international study
Authorvan den Bent, M; Gan, HK; Lassman, AB; Kumthekar, P; Merrell, R; Butowski, N; Lwin, Z; Mikkelsen, T; Nabors, LB; Papadopoulos, KP; ...
Source TitleCancer Chemotherapy and Pharmacology
AffiliationMedicine and Radiology
Document TypeJournal Article
Citationsvan 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 StatusOpen Access
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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