Depatuxizumab Mafodotin (ABT-414): A Comprehensive Analysis of an Anti-EGFR Antibody-Drug Conjugate for Glioblastoma

Molecular Architecture and Therapeutic Rationale

Introduction to an Advanced Antibody-Drug Conjugate (ADC)

Depatuxizumab mafodotin, also known by its development code ABT-414 and trade name Depatux-M, is an investigational biotech therapeutic classified as an antibody-drug conjugate (ADC).[1] ADCs represent a sophisticated class of targeted cancer therapies engineered to function as "guided missiles," selectively delivering a potent cytotoxic payload to tumor cells while minimizing exposure to healthy tissues.[3] This strategy aims to widen the therapeutic window, maximizing anti-tumor efficacy and reducing the systemic toxicity often associated with conventional chemotherapy.[3]

Developed by AbbVie (and its predecessor, Abbott), Depatuxizumab mafodotin was designed specifically to address cancers driven by aberrations in the epidermal growth factor receptor (EGFR) pathway, with a primary focus on glioblastoma (GBM), the most common and aggressive primary brain tumor in adults.[1] The significant unmet medical need in this patient population was recognized by regulatory agencies; the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) granted the compound Orphan Drug Designation for the treatment of glioblastoma in 2014.[1] Further highlighting its potential in rare, difficult-to-treat cancers, the FDA also granted it a Rare Disease Designation in 2016 for the treatment of pediatric patients with EGFR-amplified Diffuse Intrinsic Pontine Gliomas (DIPG).[3]