Safety, pharmacokinetics, and antitumor response of depatuxizumab mafodotin as monotherapy or in combination with temozolomide in patients with glioblastoma

Hui K. Gan*, David A. Reardon, Andrew B. Lassman, Ryan Merrell, Martin Van Den Bent, Nicholas Butowski, Zarnie Lwin, Helen Wheeler, Lisa Fichtel, Andrew M. Scott, Erica J. Gomez, Judee Fischer, Helen Mandich, Hao Xiong, Ho Jin Lee, Wijith P. Munasinghe, Lisa A. Roberts-Rapp, Peter J. Ansell, Kyle D. Holen, Priya Kumthekar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Background We recently reported an acceptable safety and pharmacokinetic profile of depatuxizumab mafodotin (depatux-m), formerly called ABT-414, plus radiation and temozolomide in newly diagnosed glioblastoma (arm A). The purpose of this study was to evaluate the safety and pharmacokinetics of depatux-m, either in combination with temozolomide in newly diagnosed or recurrent glioblastoma (arm B) or as monotherapy in recurrent glioblastoma (arm C). Methods In this multicenter phase I dose escalation study, patients received depatux-m (0.5-1.5 mg/kg in arm B, 1.25 mg/kg in arm C) every 2 weeks by intravenous infusion. Maximum tolerated dose (MTD), recommended phase II dose (RP2D), and preliminary efficacy were also determined. Results Thirty-eight patients were enrolled as of March 1, 2016. The most frequent toxicities were ocular, occurring in 35/38 (92%) patients. Keratitis was the most common grade 3 adverse event observed in 6/38 (16%) patients; thrombocytopenia was the most common grade 4 event seen in 5/38 (13%) patients. The MTD was set at 1.5 mg/kg in arm B and was not reached in arm C. RP2D was declared as 1.25 mg/kg for both arms. Depatux-m demonstrated a linear pharmacokinetic profile. In recurrent glioblastoma patients, the progression-free survival (PFS) rate at 6 months was 30.8% and the median overall survival was 10.7 months. Best Response Assessment in Neuro-Oncology responses were 1 complete and 2 partial responses. Conclusion Depatux-m alone or in combination with temozolomide demonstrated an acceptable safety and pharmacokinetic profile in glioblastoma. Further studies are currently under way to evaluate its efficacy in newly diagnosed (NCT02573324) and recurrent glioblastoma (NCT02343406).

Original languageEnglish (US)
Pages (from-to)838-847
Number of pages10
JournalNeuro-oncology
Volume20
Issue number6
DOIs
StatePublished - May 18 2018

Keywords

  • EGFR
  • antibody-drug conjugate
  • depatux-m
  • phase 1
  • recurrent glioblastoma

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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