EGFR is a key oncogenic target for the treatment of glioblastoma. EGFR amplification is detected in ∼50% of tumors. Depatuxizumab mafodotin (depatux-m), formerly called ABT-414, is a tumor-specific antibody-drug conjugate that preferentially targets tumors with EGFR amplification. Herein, we report the frequency of EGFR amplification in 2 large-scale glioblastoma clinical trials of depatux-m.
Assays for EGFR abnormalities were performed centrally in 2077 (as of May 1, 2017) glioblastomas during screening for 2 randomized glioblastoma trials with depatux-m: INTELLANCE 1 (NCT02573324) for newly diagnosed patients (n = 1001), and INTELLANCE 2 (NCT02343406) for recurrent disease (n = 1076). EGFR amplification, required for eligibility in both trials, was determined by fluorescence in situ hybridization and defined as at least 2 copies in at least 15% of cells. EGFRvIII data will be reported at the meeting.
The frequency of EGFR amplification was ∼50% (Table), similar to published rates. Higher rates were observed in patients from the Americas/Europe (53–57%) than from Asia (34%).Table:
327O Pooled Screening Results: INTELLANCE 1 (phase II/III, newly diagnosed) and INTELLANCE 2 (phase II, recurrent)
|World Region||Not Amplified||EGFR Amplified||Total Patients||Positive, %|
This study represents the first report of lower EGFR amplification rates in patients from Asia with glioblastoma to our knowledge. This observation requires further study.
Clinical trial identification
INTELLANCE 1: NCT02573324 INTELLANCE 2: NCT02343406
Legal entity responsible for the study
M.J. van den Bent: Honoraria from Roche, AbbVie, Celldex, Novocure, Merck Ag, Cavion, Actelion, Bristol-Myers Squibb, Blue Earth Diagnostics. Research funding from AbbVie and Roche. L.A. Roberts-Rapp, P. Ansell, J. Looman, E. Bain, C. Ocampo, K.D. Holen, E.J. Gomez: AbbVie employee and may own stock. J. Lee: Abbott employee (companion diagnostic partner). A.B. Lassman: Honoraria and/or travel support from Kadmon, AbbVie, Sapience Therapeutics, Novocure, AstraZeneca, Genentech, Bioclinica. Research funding from multiple companies including AbbVie.