Correlation of an Aurora A single nucleotide polymorphism (SNP) with clinical responses to alisertib in patients (pts) with advanced solid tumors.

2583Background: Alisertib (MLN8237) is an investigational, oral, selective Aurora A kinase inhibitor. The Aurora A gene contains two functional SNPs (codon 31 and codon 57) that modify kinase activity. We assessed prognostic and predictive value of these SNPs. Methods: We did a correlative study of the Aurora A SNPs in The Cancer Genome Atlas (TCGA) database to evaluate their association with overall survival (OS), we then further assessed their potential association with clinical responses in 2 alisertib phase 2 trials. Whole blood samples were collected prior to alisertib study commencement and pt genotypes were analyzed by PCR. In study 1 (NCT01045421), single agent alisertib was investigated in pts with advanced solid tumors; Aurora A SNP profiles of 85 pts were obtained. In study 2 (NCT01091428), a randomized trial of alisertib plus weekly paclitaxel vs paclitaxel alone in pts with advanced recurrent ovarian cancers, Aurora A SNPs were genotyped in 122 pts (62 and 60 from each arm). The link between ...