Abstract A250: ABT-414: An anti-EGFR antibody-drug conjugate as a potential therapeutic for the treatment of patients with squamous cell tumors.

Abstract

Abstract ABT-414 is an antibody-drug conjugate (ADC) comprised of an anti-EGFR antibody (ABT-806) conjugated to the potent cytotoxic monomethylauristatin F. ABT-414 binds a unique epitope of EGFR which is largely inaccessible when EGFR is expressed at physiological levels but is accessible in tumors that express EGFRde2-7 [also referred to as EGFR variant III (EGFRvIII)] and in tumors with wild-type amplified EGFR or excessive wild-type EGFR activation. These properties of ABT-414 should limit the effects of the toxin on normal tissues. ABT-414 is highly effective in both mutant and wild-type EGFR-positive human tumor xenografts in mice producing complete regressions and cures observed in the most sensitive models. Squamous cell tumors display a relatively high expression of EGFR. Immunohistochemical analysis reveals >70% of squamous lung and esophageal cancers and >90% of oral cavity tumors show moderate to strong staining for EGFR. Given the high unmet need in these patients and the in vivo data supporting improved ABT-414 efficacy in tumors with high EGFR expression, a Phase I/IIa study evaluating the safety, pharmacokinetics and efficacy of ABT-414 in subjects with EGFR-positive, refractory solid tumors has been initiated with a phase IIa expansion at the MTD in squamous NSCLC. Additionally, this study will evaluate the use of SPECT imaging with an indium-111-labeled parental antibody (ABT-806i) as a predictive tool for patient response. Tumor uptake by ABT-806i SPECT imaging correlates with antitumor response in xenograft models, and ABT-806i has been shown to effectively target tumor sites in select cancer patients. A fluorescent in situ hybridization (FISH) probe to detect EGFR amplification and EGFR IHC are also being evaluated with the goal of identifying patients who are most likely to respond to ABT-414 treatment. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A250. Citation Format: Andrew C. Phillips, Erwin R. Boghaert, Kedar S. Vaidya, Peter J. Ansell, David R. Shalinsky, Yumin Zhang, Martin J. Voorbach, Sarah Mudd, Kyle D. Holen, Rod A. Humerickhouse, Edward B. Reilly. ABT-414: An anti-EGFR antibody-drug conjugate as a potential therapeutic for the treatment of patients with squamous cell tumors. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A250.