Track 3: Advancing Cancer Therapy
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TUESDAY, SEPTEMBER 22
2:00-3:00 pm Conference Registration
3:00-3:15 Welcoming Remarks
Phillips Kuhl, Cambridge Healthtech Institute
3:15-3:45 The FDA’s Role in Improving Drug Development
Douglas C. Throckmorton, M.D., Deputy Director, Center for Drug Evaluation and Research, U.S. Food and Drug Administration
There are many pressures on the medical products endeavor, including the need for more timely and efficient development to support their marketing, and then assessment after marketing to support their best uses. There are many stakeholders with important responsibilities in the healthcare system. As regulators, the FDA has a clear role in responding to these pressures, one that includes both providing a clear path to efficient development as well as a critical role in supporting innovation and collaboration.
3:45-4:15 Oncology Clinical Trial Design: Opportunities for Rational (and Irrational) Incorporation of Biomarkers to Achieve the Goal of Individualized Therapy
Mark J. Ratain, M.D., Leon O. Jacobson Professor of Medicine; Chairman, Committee on Clinical Pharmacology and Pharmacogenomics; Associate Director, Clinical Sciences, Cancer Research Center, The University of Chicago
Biomarkers are often hailed as a panacea to reduce attrition rates of oncology drug development, thereby decreasing drug development costs. To date, the incorporation of predictive biomarkers has had mixed results, including important successes (e.g., HER2 testing for trastuzumab) and failures (e.g., EGFR testing for cetuximab). Pharmacodynamic biomarkers are similarly of theoretical value to accelerate decision-making, but in practice have had limited utility due to lack of technical validation and misconceptions of the value of a biomarker of unknown clinical importance. Novel trial designs incorporating predictive and pharmacodynamic biomarkers will be discussed.
4:15-4:45 Personalized Medicine Depends on Drug Pipeline-Efficacy Pharmacogenetics to Create New Targeted Therapies
Allen D. Roses, M.D., Jefferson-Pilot Professor of Neurobiology and Neurology; Director, Deane Drug Discovery Institute; Senior Scholar, Fuqua School of Business; Member, Duke Institute for Genome Sciences & Policy, Duke University School of Medicine
“Personalized medicine” has become a “hot topic,” discussed by many but practiced by few who are accountable for discovering and developing new medicines. I will present the viewpoint that targeted medicines that are reimbursable will drive the incentives of personalized medicine commercially. Currently academic and external investigators have the opportunity to test medicines independent of the sponsors only after they appear on the market. This creates a negative influence on drug developers in that new adverse events and focused efficacy occurs post-marketing, after a price has been set. Each reduces the potential market. Payers understand this and are willing to reimburse safe and effective medicines of value. The time to create that scenario is during drug development, especially with respect to pipeline efficacy. A medicine increases value when the “right” patients can be identified – except, when these data appear in the post-marketing period, the price never goes up with the value. Great strides in pharmaceutical development will be fueled by the prospective and integrated use of pipeline pharmacogenetics and encouragement of informational conversations with regulatory authorities, including but not limited to Voluntary eXploratory Data Submissions [VXDS].
4:45-5:15 Disease Biology as a Precompetitive Space: Emerging Opportunities for Distributed Contributors to Jointly Evolve Disease Models
Stephen H. Friend, M.D., Ph.D., President, Sage Bionetworks
Significant advances in generating probabilistic casual models as pioneered by Eric Schadt and colleagues at Rosetta Inpharmatics over the last five years have afforded an opportunity to share data not as linear files but as they reflect onto predictive models of disease. Examples will be shown that highlight the power of such models in metabolic and oncologic diseases. Emphasis will be placed on how classical target and pathway representations of disease miss capturing the essential biology needed to generate biomarkers and to develop drugs. Also to be discussed are the new organizational structures being built at the private/public interface that will allow investigators to modify and evolve each other’s models of biology. We posit that when biological data can be refl ected onto evolving disease models that clinicians and scientists in academia and industry will be able to enter into connected projects that can evolve the resolving power of disease models in ways natural to chemists but alien to most biologists.
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5:15-6:15 Grand Opening Reception in the Exhibit Hall Sponsored by
WEDNESDAY, SEPTEMBER 23
7:00 am Conference Registration Open
7:30-8:15 Breakfast Presentation
Discovering and Measuring Protein Biomarkers in FFPE Tissue
David Krizman, Ph.D., Chief Scientific Officer and Scientific Co-founder, Expression Pathology Inc.
Expression Pathology is a leader in tissue proteomics. Focusing on the gold standard in clinical tissue preservation, formalin-fixed paraffin-embedded tissue, we are developing proprietary new Liquid Tissue® MRM cancer tests for tissue protein biomarkers. Our technology has great potential in drug development, clinical trials and personalized medicine. Measuring protein expression in standard formalin-fixed tissue samples can provide diagnostic and prognostic information to guide treatment decisions.
Combining Liquid Tissue® sample preparation with Multiple Reaction Monitoring mass spectrometry enables precise, multiplex protein quantitation.
8:25-8:30 Chairperson’s Opening Remarks
Theresa LaVallee, Ph.D., Director,Translational Sciences Oncology, MedImmune
1. Combination Therapies
8:30-9:00 Combination Approaches for the Treatment of Solid Tumors: Opportunities and Obstacles in the Era of Targeted Therapy
Jon M. Wigginton, M.D., Group Medical Director, Discovery Medicine - Oncology, Bristol-Myers Squibb Co.
2. Translational Medicine: A Two-Way Street
9:00-9:30 Defining the Disease Process, from Patient to Lab to Patient
Michael N. Liebman, Ph.D., President, Managing Director, Strategic Medicine, Inc.
A critical aspect in treating patients and the ultimate development of new therapeutics and diagnostics involves understanding the complex pathway through the disease process, from risk assessment to diagnosis, treatment and outcome. Breast cancer represents a unique disease where several of these steps can be studied in terms of their impact on the overall process although many critical aspects remain unknown. The development of a roadmap that describes this disease process can be invaluable for improving patient care as well as identifying opportunities for development of new diagnostics and therapeutics.
3. Molecular Diagnostics
9:30-10:00 Enabling Personalized Medicine from FFPE Tissue
Austin Tanney, Ph.D., Scientific Liaison Manager, Almac Group
Molecular profiling and molecular diagnostics are the key to development of the prognostic and predictive tests which will usher in the era of personalized medicine. The development of such tests is often hampered by the lack of suitable tissue samples. Profiling of DNA and RNA from routinely stored formallin fixed and paraffin embedded (FFPE) tissue samples has proved to be hugely challenging. This talk provides an overview of some of the issues surrounding working with FFPE samples and how these can now be addressed. Examples will be given showing the application of RNA profiling in biomarker discovery from FFPE tissue.
4. Companion Diagnostics
10:00-10:30 Personalized Healthcare Strategies and Challenges in Oncology
Lin Wu, Ph.D., Director, Genomics & Oncology, Roche Molecular Systems, Inc.
10:30-11:30 Networking Coffee Break with Poster and Exhibit Viewing
11:30-12:00 Current Information Trends in Biomarker Research 
Jorge Manrique, Senior BioDiscovery Consultant, Thomson Reuters
Biomarkers are becoming a key tool in enhancing the productivity of pharmaceutical research & development, both in discovery and the clinic and an essential element for regulatory purposes. It will become increasingly difficult to analyze and manage the rapidly increasing information about biomarkers across all of their utilities. A new fully indexed biomarker database, BIOMARKERcenter, will help to address this problem. Using BIOMARKERcenter we will show how biomarkers mimic the lifecycle of a drug, from discovery to approval, and show the diversity of roles and techniques currently being employed in biomarker research.
Sponsored by
12:00-12:15 Analysis of Phosphorylation Sites for Biomarker Identification and the Mechanism of Kinase Inhibitors
Wei Liu, Ph.D., Wyeth Research
A custom database of more than 8,000 phosphoylation sites for 2,793 proteins from published data was constructed. Using phosphorylation patterns for PI3K and MEK inhibitors experimentally observed in EGF-stimulated A431 cells, the custom database was used to explain the activity of kinase inhibitors including identifying off-target kinases, reconstructing the phosphorylation cascade and identifying activity biomarkers. Application workflows will be described for just phosphorylation data and how integrative “omics” analysis could be structured.
Sponsored by
12:15-12:30 Integration of Proteomics, Metabolomics, and Genomics Data in GeneSpring GX Software
Pam Tangvoranuntakul, Ph.D., GeneSpring Product Manager, Agilent Technologies
Multi-assay studies are central to systems biology research. Thus, the need for software applications that support integrative data analysis becomes critical to the discovery of linkages and concordance between different data types such as genomic copy number, gene expression, proteomics, and metabolomics. This session will focus on tools in GeneSpring GX that will allow researchers to make these discoveries. Methods of integrative data analysis in GeneSpring GX will be demonstrated by comparing genomic copy number, gene expression, and proteomics data.
12:30-2:00 Lunch on your own
5. Better Cancer Models
2:00-2:30 The Use of Genetically Engineered Mice for Preclinical Testing of Novel Cancer Therapeutics
Kwok-Kin Wong, M.D., Ph.D., Associate Professor, Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Harvard Medical School
Lung cancer is the leading cause of cancer related mortality for both men and women in the United States, accounting for over 28% of all cancer deaths in 2007. Worldwide, lung cancer accounts for over one million deaths per year. Adenocarcinoma, the most common type of non-small cell lung cancer (NSCLC), now accounts for more than 40% of all lung cancer cases. Despite advances in cytotoxic drug development, radiotherapy, and patient management, the cure rate for advanced NSCLC cancer remains dismal. Recent intense efforts to define the genome of human lung adenocarcinomas have identified and validated over 50% of the oncogenic drivers in lung adenocarcinomas. In the U.S., KRAS (25%) and EGFR (10 to 15%) comprise over 40% of all activating oncogenic mutations of lung adenocarcinomas, with activating genetic alterations in HER2 (2 to 5%), BRAF (2 to 5%), PIK3CA (2 to 5%), ALK (3 to 5%) and ROS1 (1 to 3%) comprising the rest of the known oncogenic mutations. Unlike other cancer types, the oncogenic mutations in lung adenocarcinomas are thought to be mutually exclusive, as known activating oncogenic mutations rarely co-occur within the same cancer. Using the bitransgenic mouse modeling platform, we have generated inducible mouse lung cancer models that are driven by each of these oncogenic mutations. These mouse models have given valuable insights into the molecular mechanisms of lung tumorigenesis. Equally importantly, these models serve as unique platforms for testing of novel therapeutics that specifically target each of these oncogenic mutations and their associated downstream pathways.
6. Circulating Tumor Cells
2:30-3:00 Circulating Tumor Cells: From Enumeration to Comprehensive Characterization
Nicholas C. Dracopoli, Ph.D., Vice President, Biomarkers, Centocor Research & Development, Johnson & Johnson
Circulating tumor cell (CTC) enumeration has been established as a useful prognostic tool for the evaluation of patients with metastatic breast, prostate and colorectal cancer and as a predictive tool for therapeutic effectiveness in these indications. Comprehensive characterization of CTCs offers a new opportunity to obtain extensive biomarker data from tumor derived material that is otherwise unavailable using standard invasive procedures. New technologies using minimal amounts of biological templates derived from increasingly pure isolates of CTCs will, for the first time, allow individualized therapy for each patient based on the molecular pathologies detected in their CTCs.
7. Targeting The Tumor Microenvironment
3:00-3:30 Targeting Tumor Microenvironment
Suresh Mohla, Ph.D., Associate Director and Chief, Tumor Biology and Metastasis Research; Program Director, Tumor Microenvironment Network, Division of Cancer Biology, NCI
3:30-4:30 Networking Refreshment Break with Poster and Exhibit Viewing
8. Cancer Biologics
4:30-5:00 Translational Sciences in Oncology Drug Development: A Risk Mitigation Strategy
Theresa LaVallee, Ph.D., Director, Translational Sciences Oncology, MedImmune
9. Phase 0 Clinical Trials
5:00-5:30 Risk-based Compliance for Production of Agents for Phase 0 Studies
John A. Gilly, Ph.D., Deputy Director, Biopharmaceutical Development Program, SAIC-Frederick/NCI-Frederick
Exploratory IND studies (Phase 0) describe studies in patients in very early Phase I. ExpIND studies provide for an understanding between the relationship of the drug candidate and the mechanism of the disease. It also provides options to explore the biodistribution of the NME in micro-dosing studies. Many companies and academic laboratories are considering Phase 0 studies as part of their program. Important risk-based compliance decisions must be made in the development of these agents. Examples of drugs under development at the NCI will be discussed.
10. Translational Imaging
5:30-6:00 Development of a Large-Scale Multicenter Clinical Trial Network to Facilitate the Use of Imaging Biomarkers in Clinical Trials
Michael M. Graham, M.D., Ph.D., Professor of Radiology and Director, Nuclear Medicine, Department of Radiology, University of Iowa
Developers of investigational drugs have expressed a need to use investigational PET imaging biomarkers in clinical trials for the early assessment of efficacy, and also to enrich populations in subsequent large-scale trials. The SNM has obtained FDA approval for a multicenter IND for one such novel imaging biomarker, and this IND is being used for cross-reference by investigational therapeutics developers. Another major issue for sponsors attempting to complete adequate, well-controlled trials using PET imaging agents is the lack of standardization of protocols and equipment. We have developed and are using phantoms at sites registered with us (over 200 world-wide currently) to ensure and maintain imaging standardization at the clinical imaging sites. I plan to discuss the highlights of these two important developments that should facilitate multicenter trials of imaging biomarkers.
6:00 Close of Day