Plasma-based marker identification

NCI协议：9825“奥拉帕尼和西地尼尼治疗复发性卵巢癌的2期研究”

NCI Protocol: 9825 “A Phase 2 Study of Olaparib and Cediranib for the Treatment of Recurrent Ovarian Cancer” Currently there is no known biomarker that might predict for a response to the cediranib plus olaparib combination. To identify blood-based markers of anti-angiogenic inhibition, the Duke multiplex ELISA-based plasma angiome panel will be tested. This panel consists of a number of angiogenic biomarkers (Table 1), including Ang-2, stromal cell-derived factor (SDF)-1, VEGF-D, osteopontin (OPN), and interleukin (IL)-6. In order to develop the most optimal arrays, the Duke team leverages three multiplex protein array systems. Many analytes have been previously validated on the CiraScan platform, produced by Aushon Biosystems. Additional multiplex systems that will be employed include the Meso Scale Discovery (MSD) and ProteinSimple platforms. The ProteinSimple platform uses microcapillary flow cells for improved sensitivity and reproducibility versus traditional ELISA techniques. Development and optimization of an appropriately designed panel for the evaluation key angiogenic and inflammatory markers. This “Angiome” multiplex array has recently been approved by the NCI Biomarker Review Committee (BRC) as an integrated biomarker for use in two Phase III studies of cediranib and olaparib in both platinum-sensitive and platinum-resistant ovarian cancer. We worked closely with the NCI in developing our validation approach, establishing the key analytic features for protein multiplex array analyses. The Angiome multiplex array has gone through a rigorous evaluation to ensure data quality. Recently, the approach was used to identify several strong candidate predictors of benefit from bevacizumab, including VEGF-D and IL-6. Studies are underway in ovarian cancer to investigate the utility of this plasma angiome panel in directing treatment with bevacizumab and with the cediranib/olaparib combination. This approach is technically robust and readily adaptable to clinical practice. Because this data will be derived from patients, even preliminary data may significantly improve our understanding of how angiogenesis and tumor growth factors are regulated in cancer patients. Promising findings can be followed up in future clinical studies and in preclinical models. Because the Duke angiome lab serves as the core lab for multiplex ELISA analyses within the Alliance, the current ovarian cancer profiling can be compared to the profiles seen in other phase III studies, helping to optimize future profiling approaches and provide the disease specific context needed for clinically meaningful companion diagnostics. Given the results of this prior work and the work of others, we anticipate being able to identify and validate or refute candidate markers of benefit that are specific for anti-angiogenic agents.