HER-2 exon 20 YVMA insertion

In March 2019, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan (T-DXd; DS-8201)... Detection of rare mutations require sensitive and specific diagnostic assays. AmoyDx HER2 Mutation Detection Kit demonstrated robust performance in detecting representa-tive HER2 indel and single nucleotide variant mutations at low frequencies. The AmoyDx Pan Lung Cancer PCR assay showed similarly robust and sensitive detection of the common HER2 A775_G776insYVMA indel in addition to detecting clinically relevant EGFR mutations.

In 7 patients who received HER2-directed therapies, limited responses to afatinib (n=5), trastuzumab emtansine (n=3) and tucatinib (n=1) were observed and no responses were seen with immunotherapy monotherapy (n=2). The incidence of HER2-M+ is 3.1% in East Asian non-squamous NSCLC, with only 1/26 HER2ex20 overlapping with activating EGFR mutations. The clinical phenotype and genomic features of HER2ex20 tumours appear distinct from HER2other, the latter demonstrating higher TMB, co-occurring drivers and predominant non-ageing signature. The therapeutic implications of the genomic and clinical features of HER2-M+ warrant further investigation.)