Safety and efficacy of depatuxizumab mafodotin + temozolomide in patients with EGFR -amplified, recurrent glioblastoma: Results from an international phase I multicenter trial

Andrew B. Lassman*, Martin J. Van Den Bent, Hui K. Gan, David A. Reardon, Priya Kumthekar, 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, Peter J. AnsellEarle Bain, Kyle D. Holen, David Maag, Ryan Merrell

*Corresponding author for this work

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Background Patients with glioblastoma (GBM) have a dismal prognosis. Nearly all will relapse with no clear standard of care for recurrent disease (rGBM). Approximately 50% of patients have tumors harboring epidermal growth factor receptor (EGFR) amplification. The antibody-drug conjugate depatuxizumab mafodotin (depatux-m) binds cells with EGFR amplification, is internalized, and releases a microtubule toxin, killing the cell. Here we report efficacy, safety and pharmacokinetics (PK) of depatux-m + temozolomide (TMZ) in patients with EGFR-amplified rGBM. Methods M12-356 (NCT01800695) was an open-label study encompassing patients with newly diagnosed or rGBM across 3 treatment arms. Results are reported for adults with EGFR-amplified, measurable rGBM who received depatux-m (0.5-1.5 mg/kg) on days 1 and 15, and TMZ (150-200 mg/m 2) on days 1-5 in a 28-day cycle. Patients were bevacizumab and nitrosourea naïve. Results There were 60 patients, median age 56 years (range, 20-79). Fifty-nine patients previously received TMZ. Common adverse events (AEs) were blurred vision (63%), fatigue (38%), and photophobia (35%). Grades 3/4 AEs were split between ocular and non-ocular AEs, occurring in 22% of patients each. Systemic PK exposure of depatux-m was dose proportional. The objective response rate was 14.3%, the 6-month progression-free survival rate was 25.2%, and the 6-month overall survival rate was 69.1%. Conclusions Depatux-m + TMZ displayed an AE profile similar to what was described previously. Antitumor activity in this TMZ-refractory population was encouraging. Continued study of depatux-m in patients with EGFR-amplified, newly diagnosed, or recurrent GBM is ongoing in 2 global, randomized trials (NCT02573324, NCT02343406).

Original languageEnglish (US)
Pages (from-to)106-114
Number of pages9
JournalNeuro-oncology
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2019

Keywords

  • ABT-414
  • EGFR amplification
  • antibody-drug conjugate
  • depatux-m
  • rGBM

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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    Lassman, A. B., Van Den Bent, M. J., Gan, H. K., Reardon, D. A., Kumthekar, P., 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., ... Merrell, R. (2019). Safety and efficacy of depatuxizumab mafodotin + temozolomide in patients with EGFR -amplified, recurrent glioblastoma: Results from an international phase I multicenter trial. Neuro-oncology, 21(1), 106-114. https://doi.org/10.1093/neuonc/noy091