An Exploratory Study of ABT-806, a Tumor-Specific Anti-EGFR Antibody, in Subjects with Recurrent or Metastatic Head and Neck and Other Squamous Cell Carcinomas

Introduction: Despite their benefit, current anti-EGFR therapies are limited by narrow efficacy profiles due to dose-limiting toxicities. This phase 2 open-label study evaluated the efficacy and safety of ABT-806, an EGFR-targeting antibody that is tumor specific, in patients with advanced EGFR-expressing tumors including head and neck cancers (H&NC) and squamous cell carcinoma (SCC) of other sites. Methods: Patients with advanced H&NC (cohort A) or SCC of other sites (cohort B) were enrolled in the study. ABT-806 was administered as monotherapy at a dose of 24 mg/kg intravenously using a twice weekly dosing schedule until unacceptable toxicity and/or evidence of disease progression. Adverse events (AEs) were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0; tumor response was assessed using the Response Evaluation criteria in Solid Tumors v1.1. EGFR status was assessed with mAb806 and EGFRvIII immunohistochemistry and correlated with outcomes. Results: ABT-806 was well tolerated with no grade 3+ treatment-related AEs. Disease stabilization was observed in two patients (14%) and for a median duration of 19.5 weeks. This included one patient from cohort A and one patient from cohort B. Progression-free survival and overall survival was not significantly different between the two cohorts. Conclusions: Although clinical activity was limited in this small, heavily pre-treated, and biomarker-unselected population, ABT-806 demonstrated an excellent safety profile with minimal classical EGFR-related toxicity. These findings support the development of more tumor-specific EGFR antibodies for use, particularly in combinatorial regimens.