MRI apparent diffusion coefficient in a murine orthotopic glioblastoma model as a clinically translatable early readout of efficacy for AMG 595, an antibody drug conjugate targeting EGFRvIII.

11095 Background: Epidermal growth factor receptor variant III (EGFRvIII) is a constitutively active mutant of EGFR present in thirty to fifty percent of glioblastoma (GBM) patients. AMG 595, currently in Phase I trials, is composed of a fully human anti-EGFRvIII-specific antibody conjugated to the maytansinoid DM1 via a non-cleavable linker. The MRI apparent diffusion coefficient (MRI ADC) has been shown to correlate with tissue cellularity, and changes in MRI ADC can be an early indicator of therapeutic efficacy. The aim of this work is to evaluate MRI ADC as a clinically translatable early readout of tissue changes due to AMG 595 treatment in a murine orthotopic GBM model. Methods: D317 human GBM cells were intracranially injected into in female CB17 SCID mice at Day 0. Mice were randomized at Day 7, using tumor volumes calculated by MRI, and were treated with vehicle, 6.5, 11, or 22 mg/kg AMG 595 i.v. twice per week, or temozolomide 10 mg/kg p.o. daily five days per week (N=8/group). MRI was repeated ...