Abstract 4531: Development of a companion diagnostic assay for the detection of phosphatase and tensin (PTEN) protein loss and treatment with ipatasertib in metastatic castration-resistant prostatic cancer (mCRPC)

Background: Ventana Medical Systems, Inc. is developing in collaboration with Genentech, Inc., an immunohistochemical (IHC) companion diagnostic to aid in selecting patients with metastatic castration-resistant prostate cancer (mCRPC) that may benefit from ipatasertib, an Akt inhibitor therapy. The phosphatase and tensin (PTEN) protein plays an important role in controlling cell survival and cell cycle progression as a negative regulator of the phosphoinositide 3-kinase/AKT pathway. Methods: PTEN (SP218) rabbit monoclonal primary antibody was optimized for use with the VENTANA OptiView DAB IHC Detection Kit on the automated BenchMark ULTRA platform (PTEN (SP218) RxDx Assay). The PTEN (SP218) RxDx Assay was developed for use in formalin-fixed, paraffin-embedded tissue samples of mCRPC in a series of studies addressing sensitivity, specificity, robustness and precision. The scoring algorithm was defined using statistical analysis of clinical outcome data analysis, and the PTEN (SP218) RxDx Assay staining pattern and prevalence of PTEN loss of expression in a set of tissue samples. Inter-reader precision was established by 3 pathologists evaluating 90 mCRPC samples across the range of PTEN expression levels. Results: The Ventana PTEN (SP218) RxDx Assay met all pre-defined acceptance criteria. mCRPC tissue samples are designated with PTEN-Loss status when ≥ 50% of viable malignant cells have no specific cytoplasmic staining with PTEN (SP218) in the presence of acceptable internal controls. Inter-reader precision in determining PTEN status resulted in agreement rates greater than 97%. Conclusion: These results highlight the robustness and reproducibility of the Ventana PTEN (SP218) RxDx Assay. In the clinical outcome analysis, patients identified to have PTEN-loss status demonstrated clinically meaningful improvements when treated with ipatasertib. The clinical utility of the PTEN (SP218) RxDx assay will be further validated in additional patients in subsequent ipatasertib studies, including a Phase 3 study (IPATential150) beginning in 2017. Citation Format: Crystal Stephens, Erica Harnish, Rebecca Bowermaster, Azita Djalilvand, Dustin Smith, Doris Kim, Steven Gendreau, Edmundo Del Valle. Development of a companion diagnostic assay for the detection of phosphatase and tensin (PTEN) protein loss and treatment with ipatasertib in metastatic castration-resistant prostatic cancer (mCRPC) [abstract]. In: Proceedings of the American Association for Cancer Research An