Introduction: Epidermal growth factor receptor (EGFR) is overexpressed in up to 90% of head and neck squamous cell carcinomas (HNSCCs). As such, EGFR is a potential target for antibody-drug conjugates (ADCs). Depatuxizumab mafodotin (depatux-m, ABT-414), is an EGFR-targeting ADC comprised of the monoclonal antibody (mAb) ABT-806 paired with monomethyl auristatin F, a tubulin polymerization inhibitor. ABT-806 selectively binds to a unique conformation of human EGFR that is expressed in cancers due to EGFR overexpression, gene amplification, or a mutant form of EGFR with deletions of exons 2 through 7. The goal of this study is to measure the safety and efficacy of ABT-414 on HNSCCs.

Methods: The effects of ABT-414 on HNSCCs were determined via cytotoxicity assays and in vivo mouse models, both using human HNC cell lines. We further investigated the distribution of ABT-414 through labeling the antibody with IRDye 800CW (Ex/Em: 774/789 nm) and analyzed the antibody’s localization ex vivo.

Results: Exposure to ABT-414 in vitro facilitated cell death in an immunocompromised mouse xenograft model, with four doses of 4 mg/kg of drug given every four days yielding antitumor activity in the high EGFR-expressing HNSCC cell line FaDu (p= 0.023) without change in body mass (p= 0.1335). The lower EGFR-expressing cell line UMSCC47 yielded a similar trend, though the results were not significant (p = 0.1761). Molecular imaging demonstrated ABT-414-IRDye800 accumulation in the tumor, with a signal to background ratio of 27.4.

Conclusions: ABT-414 treatment yielded antitumor activity in the high EGFR-expressing HNSCC cell line FaDu, although not in UMSCC47, highlighting the potential for ABT-414 efficacy in high EGFR-expressing HNSCC tumors. Furthermore, ex vivo data suggested that ABT-414 could prove efficacious in treating other EGFR-expressing cancers.