DEPATUXIZUMAB MAFODOTIN Anti-EGFR antibody-drug conjugate Treatment of glioblastoma multiforme MONOGRAPH

Depatuxizumab mafodotin (ABT-414) is an antibody-drug conjugate (ADC) comprised of the anti-epidermal growth factor receptor (EGFR) antibody ABT-806, conjugated to the potent cytotoxic monomethylauristatin F. This new ADC targets a unique tumor-specific epitope only expressed in activated wild-type EGFR and in the EGFRde2-7 (EGFRvIII) deletion mutant, both of which are frequently amplified in glioblastoma multiforme (GBM). Both in vitro and in vivo, ABT-414 has demonstrated the ability to inhibit the growth of tumors with high EGFR expression, leading to complete regression in some of the most sensitive models. ABT-414 has also shown activity in tumor models with EGFR mutations, including activating mutations and EGFRvIII deletion mutations. In phase I trials, ABT-414 demonstrated a unique safety profile and promising antitumor activity in solid tumors and GBM with EGFR amplifications. ABT-414 is currently in phase II clinical trials for the treatment of GBM.