Pre-Conference Events:
MONDAY, JANUARY 26
8:30-12:00 Registration for Pre-Conference Events*
11:00-3:00 Pre-Conference Tutorial*
(*Separate Registration Required)
Fit-for-Purpose Biomarker Assay Development and Validation
Instructors:
Jean Lee, Ph.D., Scientific Director, PKDM, Amgen
Viswanath Devanarayan, Ph.D., Director, Statistics, Biomarker Research, Abbott Laboratories
John Allinson, FIBMS, Laboratory Director, Veeda Clinical Research
This tutorial will provide recommendations on the “fit-for-purpose” best practices in the development and validation of biomarker assays for the intended exploratory or advanced biomarker applications. Strategies for different applications at various phases of biomarker development will be described. Key elements in the method development and validation will be illustrated with examples, including reference to standard material, sample stability and collection integrity, validation and QC samples, validity of reference standards, calibration curve fitting methods, method optimization and method feasibility studies. The special challenges in protein biomarker assays will be discussed, including strategies for moving from biomarker panels in the exploratory phase to the few markers chosen to support clinical trials.
Outline:
Introduction - Nomenclature, types of biomarker methods/assays, biomarker method development & validation road map, fundamental validity, similarity and differences from PK assays & diagnostic application.
Pre-analytical and bioanalytical elements: Target range, standards, validation & QC samples, stability, matrix effect, specificity, and relative selectivity.
Calibration curve model selection, evaluation, and weighting.
Method feasibility and optimization with precision profiles.
Evaluation of some pre-study validation characteristics such as precision, bias, sensitivity and quantification limits.
Use of Sample Controls for in-study performance monitoring and conformance testing among laboratories.
9:00-3:00 Pre-Conference Workshop*
(*Separate Registration Required)
Novel Cancer Biomarkers
9:00-9:05 Chairperson’s Opening Remarks
9:05-9:30 in vivo Discovery and Validation of Biomarkers of Human Drug Response and Resistance
Joerg Heyer, Ph.D., Principal Scientist, Group Leader, Genetic Models, AVEO Pharmaceuticals, Inc.
With the emerging elucidation and understanding of the human genome, the complexities of genetic changes in cancer have become apparent. Traditional models of preclinical research and development have generally not recapitulated the dynamics of the genome found in cancer. New approaches to genetically engineered models, i.e. exploiting the natural diversity of signaling pathways in genetically engineered cancer models, or generating spontaneous human tumors in tissue transplantation models, have shown great promise to faithfully capture the complexity of genomic changes seen in cancer. We have generated a Human Response Prediction approach, based on naturally occurring variation in our genetically defined models of cancer, which allows us to identify genetic biomarkers of therapeutic response.
9:30-9:55 Preclinical Biomarker Discovery and Validation for a Small Molecule Inhibitor of MEK Kinase
Mark R. Lackner, Ph.D., Scientist, Developmental Oncology Diagnostics, Genentech, Inc.
Abstract unavailable at the time of printing.
9:55-10:25 Networking Coffee Break
10:25-10:50 Circulating HER-2/neu, A Biomarker for HER-2 Positive Breast Cancer, from Discovery to Patient Management
Walter Carney, Ph.D., Head, Oncogene Science, Siemens Healthcare Diagnostics, Inc.
Pharmaceutical companies are developing a large number of targeted oncology therapies that will require specific biomarker tests or targeted diagnostics to guide the use of these agents. This presentation will provide an overview and update on the serum HER-2/neu test, which is a specific biomarker for HER-2 positive breast cancer. The serum HER-2/neu test measures the extracellular domain (ECD) of the HER-2/neu oncoprotein in the blood of breast cancer patients. The test is used clinically to measure the rise and fall of the ECD which parallels clinical course of disease. Since the test specifically measures the circulating ECD, it is used to monitor the response or lack of response of the HER-2 positive tumor exposed to a variety of therapies, including hormone therapy, chemotherapy, and Herceptin/chemotherapy of Tykerb monotherapy.
10:50-11:15 Discovery of miRNA-Based Biomarkers for Cancer
Søren Møller, Ph.D., Vice President, Research and Development, Exiqon A/S
Abnormal expression of microRNAs (miRNAs) in cancer implies that these small ~22-nucleotide molecules play a role in oncogenesis. Therefore miRNAs may comprise a novel class of diagnostic and prognostic signatures. This talk will focus on examples of using microRNA for cancer classification, prognosis and treatment selection.
11:15-12:30 pm Lunch on your own
12:30-12:55 Cancer Biomarker Discovery in the Context of Personalized Medicine
Josip Blonder, M.D., Senior Research Scientist, Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick Inc., NCI-Frederick
The major goal of oncoproteomics is the discovery of clinically relevant molecular biomarkers. So far, the translation of proteomic assays to applicable diagnostic and/or prognostic tests in clinical oncology and personalized medicine has been disappointing. We developed an innovative proteomic platform for cancer biomarker discovery that is amenable to personalized medicine since all specimens were obtained from a single patient, diagnosed with renal cell carcinoma. This approach relies on concurrent profiling of peripheral serum/plasma specimens obtained prior to surgery coupled with subtractive analysis of non-tumorous and tumorous tissue samples procured after the surgical intervention. Multidimensional shotgun proteomic analysis, rigorous bioinformatic data processing coupled with orthogonal validation was employed to narrow the selection/panel of potential renal cancer biomarker proteins.
12:55-1:20 Industrialized Proteomics for the Discovery and Validation of Oncology Biomarkers
Daniel Chelsky, Ph.D., Chief Science Officer, Caprion Proteomics
The success of many investigational drugs is dependent on matching treatments with the appropriate target populations. Variability in response to therapy, both with regards to efficacy and to adverse events, is leading the pharmaceutical industry down the path of personalized medicine. Further pushing the process along are government and private insurance payors who are faced with very expensive treatments that can help some but provide little benefit and possible harm to others. One promising solution to the problem is to identify predictive biomarkers of drug efficacy; circulating proteins that stratify patients into populations of likely responders and non-responders to a proposed therapy. Finding such biomarkers has been challenging due to the complexity of human plasma, the sample of choice, and to the available technologies for detection and quantification of thousands of proteins. Based on the experience of over two dozen preclinical and clinical proteomic studies with pharmaceutical partners, an “industrialized” and very productive approach to biomarker discovery and validation has been developed. Results from multiple oncology biomarker discovery studies will be presented that make the case for accelerating the move to personalized medicine.
1:20-1:45 Metabolite Biomarkers of Prostate Cancer Aggressivity
Jeffrey Shuster, Ph.D., Director, Diagnostics Development, Metabolon, Inc.
Even with all the diagnostics methods in use today, it is difficult to determine with surety which prostate cancers are indolent, and which are aggressive and have the potential to metastasize. Diagnostic tests that distinguish indolent from aggressive tumors have the potential to reduce the number of unnecessary biopsies and prostatectomies. Prostate cancer aggressivity was investigated at the biochemical level using metabolomics with urine from men at-risk for prostate cancer, and from post-surgical prostate tissue. The results identified sets of mechanism-based biomarkers correlated with prostate cancer aggressivity. In this talk, we will briefly describe the metabolomics platform and its utility for developing cancer diagnostics.
1:45-2:10 Networking Refreshment Break
2:10-2:35 From Discovery to the Clinic: The Novel DNA Methylation Biomarker, Septin 9, for the Detection of Colorectal Cancer in Blood
Shannon Payne, Ph.D., Senior Scientist, Epigenomics, Inc.
Detection of colorectal cancer (CRC) at early stages has been shown to greatly decrease mortality from the disease. Availability of a blood-based test for CRC is expected to improve screening compliance in the general population. Through DNA methylation-sensitive, restriction enzyme-based biomarker discovery we identified a region of the Septin 9 gene that is methylated in over 90% of colorectal cancer tissues with little or no methylation in normal colon tissue and other controls. Using a systematic method of biomarker development, we demonstrated specific detection of CRC DNA using the Septin 9 methylation biomarker in multiple studies of plasma from CRC patients and controls. A prospective clinical trial is now underway to determine the clinical performance of the Septin 9 biomarker in the CRC screening-eligible population.
2:35-3:00 Multiplexed Analysis of Glycan Variation on Serum Proteins Using An Antibody Array for Biomarker Profiling
Bryce P. Nelson, Ph.D., Vice President, Research and Development, Gentel Biosciences
Protein glycosylation is a critical determinant of protein function, but there is a lack of tools for discovery and validation of the glycosylation of specific proteins for use as biomarkers. We have developed a 46-plex antibody array in a 96-well format to measure changes in both the glycosylation and concentration of specific cancer biomarker proteins in patient serum samples. To do this, an array of antibodies captures specific proteins from serum and the glycosylation of captured proteins is measured using one of eight unique biotinylated lectins. Chemical derivatization of the glycans on the spotted antibodies prevents lectin binding to those glycans. Relative abundance of serum proteins is measured on a separate antibody array after labeling with a universal conjugate. By profiling both protein and glycan variation in multiple serum samples using parallel protein abundance and glycan-detection assays, new disease-associated glycan alterations can be identified and validated for use as biomarkers.
3:00 Close of Workshop