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BACKGROUND  Epidermal growth factor receptor ( EGFR ) alterations are associated with multiple cancers. Current EGFR‐directed therapies have led to increased efficacy but are associated with specific side effects. The antibody‐drug conjugate depatuxizumab mafodotin (depatux‐m) targets EGFR with a monoclonal antibody linked to a cytotoxin, and is highly tumor‐specific.    METHODS  This phase 1/2 study evaluated the safety, pharmacokinetics, and efficacy of depatux‐m in patients who had advanced solid tumors with known wild‐type  EGFR  overexpression, amplification, or mutated  EGFR  variant III. A 3 + 3 dose escalation was used, and 2 dosing schedules were evaluated. Depatux‐m also was manufactured under an alternate process to reduce the drug load and improve the safety profile, and it was tested at the maximum tolerated dose (MTD). In another cohort, prolonged infusion time of depatux‐m was evaluated; and a cohort with confirmed  EGFR  amplification also was evaluated at the MTD.    RESULTS  Fifty‐six patients were treated. The MTD and the recommended phase 2 dose for depatux‐m was 3.0 mg/kg. Common adverse events (AEs) were blurred vision (48%) and fatigue (41%). A majority of patients (66%) experienced 1 or more ocular AEs. Grade 3 or 4 AEs were observed in 43% of patients. One patient with  EGFR ‐amplified, triple‐negative breast cancer had a partial response. Stable disease was observed in 23% of patients. Pharmacokinetics revealed that depatux‐m exposures were approximately dose‐proportional.    CONCLUSIONS  Depatux‐m resulted in infrequent nonocular AEs but increased ocular AEs. Patient follow‐up confirmed that ocular AEs were reversible. Lowering the drug‐antibody ratio did not decrease the number of ocular AEs. A partial response in 1 patient with  EGFR ‐amplified disease provides the opportunity to study depatux‐m in diseases with a high incidence of  EGFR  amplification.   Cancer  2018;124:2174‐83 . ©  2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.  This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

cancer

Efficacy and safety results of depatuxizumab mafodotin (ABT‐414) in patients with advanced solid tumors likely to overexpress epidermal growth factor receptor