Evaluation of a novel RNA biomarker of CDK2 inhibition in phase 1 clinical trials with BMS-387032

2031 Background: BMS-387032 is a potent and selective inhibitor of CDK2 with demonstrated activity in several preclinical models. A biomarker for CDK2 inhibition with BMS-387032 was identified in previous transcription profiling experiments in which A2780 human ovarian tumor cells were treated with BMS-387032 or antisense oligonucleotides that target CDK2, human PBMCs were treated with BMS-387032, and A2780 tumor xenografts were treated with BMS-387032. Of ∼300 genes which were regulated, the W28729 gene, was consistently induced. Thus, the W28729 gene was selected for further evaluation in the initial phase I clinical trials with BMS-387032. Methods: Whole blood samples were collected for W28729 expression analyses from 3 ongoing phase I trials evaluating BMS-387032 administered iv as either a 1 h infusion q3 weeks, 24 h infusion q3 weeks, or 1 h infusion q week. Blood samples were obtained prior to and periodically during BMS-387032 treatment. RNA extracted from whole blood was analyzed for W28729 expre...