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


  • 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/m2) 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).


  • Lassman, Andrew B
  • van den Bent, Martin J
  • Gan, Hui K
  • Reardon, David
  • Kumthekar, Priya
  • Butowski, Nicholas
  • Lwin, Zarnie
  • Mikkelson, Tom
  • Nabors, Louis B
  • Papadopoulos, Kyriakos P
  • Penas-Prado, Marta
  • Simes, John
  • Wheeler, Helen
  • Walbert, Tobias
  • Scott, Andrew M
  • Gomez, Erica
  • Lee, Ho-Jin
  • Roberts-Rapp, Lisa
  • Xiong, Hao
  • Ansell, Peter J
  • Bain, Earle
  • Holen, Kyle D
  • Magg, David
  • Merrell, Ryan

publication date

  • 2019

has subject area