Abstract A046: Pre-clinical assessment of neratinib sensitivity and biomarkers of response

Introduction: Neratinib is an irreversible pan-HER inhibitor that has shown clinical activity against HER2-amplified (HER2+) and HER2-mutated cancers. Alteration in HER2 is currently the only biomarker of sensitivity to neratinib. To examine other potential biomarkers of sensitivity, we evaluated neratinib as a single agent in a panel of 108 cancer cell lines from 25 different primary tumour sites. In order to determine possible biomarkers of response, correlation analysis was performed to assess the relationship between genomic alterations or gene expression levels of oncogenes and neratinib response. Methods: Sensitivity to neratinib was assessed in 108 cancer cell lines (Oncolines™) by ATPlite assay after 72-hour treatment. Pearson correlation analysis was carried out between the gene expression profile of 361 relevant cancer genes for 94 of the 108 cell lines (CCLE) and neratinib sensitivity (10logIC50 values). The neratinib gene expression profile was then compared to u003e 160 reference compound profiles to exclude false positives. The mutation and copy number status of established oncogenes and tumour suppressor genes was sourced from COSMIC cell lines project and CCLE and compared to neratinib IC50 values by ANOVA and t-test. Results: Neratinib had a potent anti-proliferative effect across numerous cancer types, achieving an IC50 value of Citation Format: Neil T Conlon, Jeffrey J Kooijman, Guido JR Zaman, Irmina Diala, Alshad Lalani, John Crown, Denis M Collins. Pre-clinical assessment of neratinib sensitivity and biomarkers of response [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A046. doi:10.1158/1535-7163.TARG-19-A046