Abstract 3749: Single agent activity of PIK3CA inhibitor BYL719 in a broad cancer cell line panel

NVP-BYL719 is a p110α isoform-specific small molecule inhibitor that is currently in a Phase I clinical trial. To identify cancer populations that most likely to respond to BYL719 treatment, we initiated a comprehensive in vitro pharmacologic profiling screen across a large panel of cancer cell lines that have been previously characterized at the molecular level as part of the Cancer Cell Line Encyclopedia (CCLE) effort. We found that BYL719 responsive cell lines are enriched in indications such as Her2 positive and luminal breast cancer, while lacking in other indications such as Glioblastoma and Melanoma. Further exploration of the underlying genetic and pathway aberrations revealed that BYL719 sensitivity is positively associated with PIK3CA mutation, ERBB2 amplification and PIK3CA amplification/copy number gain. PTEN and BRAF mutations on the other hand, are associated with BYL719 insensitivities. KRAS mutation alone is neither associated with enhanced sensitivity nor insensitivity, however, co-commitant PIK3CA and KRAS mutants are more likely to be insensitive to BYL719 treatment. These findings will help to guide our clinical development plan. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3749. doi:1538-7445.AM2012-3749