Abstract 914: Activity of SGN-B6A in patient-derived xenograft models of non-small cell lung cancer

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 expressed constitutively at low levels in numerous epithelial tissues and induced by tissue injury due to its role in tissue remodeling and wound repair. Numerous solid tumors, including non-small cell lung cancer (NSCLC), have been reported to overexpress integrin beta-6. Its role in tissue remodeling is believed to be the function that malignant cells exploit through its overexpression, allowing them to become more invasive into surrounding healthy tissue. Integrin beta-6 has also been reported to be among the integrins that can promote the epithelial to mesenchymal transition as well as provide resistance to anoikis, thus increasing the metastatic potential of malignant cells expressing it. SGN-B6A is an investigational antibody-drug conjugate (ADC) targeting integrin beta-6 to deliver the clinically validated payload monomethyl auristatin E (MMAE). We have previously presented data illustrating the antitumor activity of SGN-B6A in cell line-derived xenograft models originating from multiple carcinoma indications. Here we present results from a study of SGN-B6A activity dosed weekly at 3 mg/kg in patient-derived xenograft models of NSCLC, representing both squamous and adenocarcinoma histology. These results suggest that SGN-B6A is a promising ADC for the treatment of NSCLC and support further clinical investigation in the ongoing Phase I study (NCT04389632). Citation Format: Robert P. Lyon, John J. Gosink, Christopher J. Hale, Jackie L. Stilwell, Sean Allred, Kelly M. Hensley, Vineet Kumar, Gabby Patilea-Vrana, Natalya Nazarenko. Activity of SGN-B6A in patient-derived xenograft models of non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 914.