Abstract A32: Accelerating biomarker discovery for companion diagnostics through mouse trials with PDX models in clinical settings

Abstract

Abstract Companion diagnostics are assays intended to find the right drug for the right patient in targeted cancer therapy. Biomarker discovery is the first step in companion diagnostics development. Currently great efforts have been devoted to biomarker discovery and validation through analysis of clinical samples. However, the quantity and quality of tumor samples from drug candidate treated patients are very limited during drug development, which has posed challenges for fast and cost-effective drug-diagnostic co-development. Patient derived xenograft (PDX) tumor models have been demonstrated to represent cancer complexity and heterogeneity known in patients. Drug targets and responses to targeted drugs in PDX models show high correlation to those in cancer patients. We have established over 950 PDX tumor models and around 100 resistance models to drugs of interest. To evaluate mouse trials with PDX models as biomarker discovery platform, we have been testing PDX models with SOCs and clinical drug candidates such as targeted inhibitors against FGFRs, c-Met/ALK, HER2, EGFR, cell cycle regulators, Ras/Raf pathway, PI3K/Akt pathway, as well as chemotherapy drugs in a biomarker-driven multi-drug multi-arm clinical trial setting, and have accumulated more than 1500 data sets and associated PD samples. Through analysis of drug response data and genomic profile data from PDX models, we show that many of the drug sensitivity biomarkers and drug resistance biomarkers identified in clinical studies can be faithfully found in PDX studies. Moreover, some novel predictive biomarkers for candidate drugs in relatively early clinical stage have also been identified and will be further validated in future clinical studies. The availability of a large number of PDX models, the flexibility of designing studies and the quickness in testing new drug candidates make this type of mouse trial and its derived data sets a useful platform for biomarker discovery in companion diagnostics development. Citation Format: Jingjing Jiang, Tengfei Yu, Ying Yan, Wei Du, Tingting Tang, Xuqin Yang, Jiali Gu, Liang Hua, Xin Katherine Ye, Zhenyu Gu. Accelerating biomarker discovery for companion diagnostics through mouse trials with PDX models in clinical settings. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A32.