Abstract
Abstract The integrins are a large family of cell surface receptors with diverse roles in cellular adhesion, motility, and cytokinesis. Functional integrins exist as heterodimers consisting of single alpha and beta chains. Within this family, integrin beta-6 (which dimerizes exclusively with isoform alpha-v) is of particular note for its role in cancer. Integrin beta-6 is overexpressed in numerous solid tumors and multiple investigators have noted its expression as a negative prognostic indicator in diverse cancers including colorectal, non-small cell lung, gastric, and cervical. SGN-B6A is an antibody-drug conjugate (ADC) targeting integrin beta-6 to deliver the clinically validated payload monomethyl auristatin E (MMAE). The antibody component of SGN-B6A is specific for integrin beta-6 and does not bind other alpha-v family members. In preclinical studies, this ADC has demonstrated activity in vivo in models derived from pancreatic, pharyngeal, and bladder carcinomas spanning a range of antigen expression levels at doses of 1 or 3 mg/kg given weekly for three doses. In exploratory toxicology studies in cynomolgus monkeys, doses of up to 5 mg/kg weekly for three doses or 6 mg/kg every 3 weeks for two doses were tolerated. Hematologic toxicities typical of MMAE ADCs were dose limiting and no evidence of target-mediated toxicity was observed. A Phase I first-in-human study is planned to evaluate the safety and antitumor activity of SGN-B6A in a variety of solid tumors known to express integrin beta-6. Citation Format: Robert P. Lyon, Michael W. Schmitt, Mechthild Jonas, Christopher E. Franz, Esther S. Trueblood, Roma Yumul, Lori Westendorf, Maureen C. Ryan. SGN-B6A: A new MMAE ADC targeting integrin beta-6 in multiple carcinoma indications [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2906.
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