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WEDNESDAY, JANUARY 28
8:00 Sponsored Presentation (Opportunity Available) or Morning Coffee
Contact Ilana Schwartz, Manager, Business Development, at 781-972-5457 or ischwartz@healthtech.com.
CASE STUDIES IN ONCOLOGY DRUG DEVELOPMENT
VECTIBIX
9:00-9:30 The KRAS Signaling Pathway Biomarker in Oncology: From Prognostic to Predictive
Scott D. Patterson, Executive Director, Medical Sciences, Amgen, Inc.
There are a number of biomarkers that are considered to be prognostic, although the difficulty in proving this with the array of treatment options available makes confirmation difficult. In some cases these same biomarkers may be predictive of response to specific therapies. Demonstration of this requires analysis of samples from clinical studies with control arms – often not employed until phase 3. Our experience in the elucidation of KRAS as a patient stratification biomarker will be presented.
VANDETANIB
9:30-10:00 Pretreatment Circulating VEGF Levels as A Predictive Biomarker of Efficacy in NSCLC Patients Treated with Vandetanib
Anderson Ryan, Ph.D., Principle Translational Scientist, Cancer BioScience, AstraZeneca
Vandetanib has demonstrated improvements in progression-free survival (PFS) in advanced NSCLC in three randomized phase II studies: vandetanib versus gefitinib; docetaxel ± vandetanib; carboplatin and paclitaxel (CP) ± vandetanib. We performed an exploratory analysis of the relationship between baseline circulating VEGF concentrations and PFS and OS. These analyses suggest that low baseline circulating VEGF may be predictive of PFS and OS advantage in patients with advanced NSCLC receiving vandetanib versus gefitinib, or vandetanib + docetaxel versus docetaxel. Notably, patients with low VEGF levels had similar outcome with either vandetanib monotherapy or CP doublet chemotherapy raising the possibility that this test could be used to select patients for treatment with a targeted therapy instead of treatment with a standard cytotoxic chemotherapy regimen.
SUNITINIB
10:00-10:30 Guidance Toward Sunitinib Clinical Development Strategy through Translational Research Approaches
James Christensen, Ph.D., Director, Translational Pharmacology, Pfizer Global Research and Development
Sunitinib malate is an approved agent for treatment of advanced renal carcinoma and/or imatinib refractory gastrointestinal stromal tumors. Efforts are ongoing to develop sunitinib in additional oncology indications including combination studies with a variety of conventional chemotherapeutic agents as well as targeted therapies. Insight towards utility of clinical biomarkers of patient benefit, prospective patient selection strategies, and novel combination approaches are warranted to continue to optimize the clinical development strategies. To this effect, ongoing activities to study sunitinib in both a lab-based and clinical setting to provide insight toward the sunitinib clinical development program will be presented.
10:30-11:30 Coffee Break with Poster and Exhibit Viewing
TARCEVA
11:30-12:00 Incorporation of Biomarkers into Tarceva Clinical Trials
Frank Richardson, Senior Director, Preclinical Safety Assessment and Molecular Markers, OSI Pharmaceuticals, Inc.
Tarceva is an EGFR tyrosine kinase inhibitor approved as monotherapy for the treatment of 2nd-3rd-line advanced non-small cell lung cancer (NSCLC) and in combination with Gemzar for the treatment of 1st-line advanced pancreatic cancer. There is intense interest in finding and validating new biomarkers that predict outcome to Tarceva and thus enhance clinical benefit. The development of biomarkers is a challenging process in which the promise of a specific biomarker can grow or diminish as new information becomes available. This talk will discuss and present preliminary results of two biomarker-selected trials in NSCLC as case examples that highlight ongoing efforts to incorporate and clinically validate emerging biomarkers in an ever-shifting landscape.
Sponsored by
12:00-12:15 Sponsored Presentation
Sponsored by
12:15-12:30 Development of Clinically Relevant Gene Expression Profiles for Prognosis of Early Stage Breast Cancer
Richard A. Bender, MD, FACP, Vice President and Chief Medical Officer, Agendia, Inc.
Gene Expression Profiling is rapidly becoming the new frontier for the development of biomarkers for the diagnosis of disease, for the assessment of prognosis and for the prediction of the liklihood of responding to a particular drug or class of drugs. The ability to analyze patient groups with multi-gene profiles using either RT-PCR or microarray oftentimes belies the complexity of the clinical question and is subject to overfitting the data as many genes are used to discriminate between 2 groups of patients , oftentimes simply responders or non-responders, "low" risk or "high" risk or disease present or absent groups. As such, meticulous attention to all experimental details from extraction of genomic material from patient specimens to interpretation of gene expression, experimental details must be rigidly controlled. As interpretation of the multi-gene readout is not intuitive" to the ordering physician (unlike a single analyte assay, such as CA 27-29) requiring a "black box" mathematicalalgorithm to generate or risk profile or result, the FDA has issued IVDMIA Guidiance for the Industry suggesting how these assays need to be regulated. The presentation will discuss the process of assay development for breast cancer prognosis as a way of illustrating the key steps in this process and will review the latest developments in governmental oversight.
12:30-2:00 Lunch on Your own
TRANSLATION FROM IN-HOUSE DEVELOPMENT TO
CLINICAL LABORATORY
(Shared session with Biomarker Assay Development meeting)
2:00-2:30 Development and Integration of Biomarkers into Clinically Useful Diagnostics
Anne-Marie Martin, Ph.D., Director, Oncology, MDC, GlaxoSmithKline
With the advancement of understanding the molecular basis of disease we have increased our ability to identify genomic biomarkers relevant to disease pathogenesis and widened opportunities to develop genomics-based tools to tailor treatment options and assess treatment response. Thus, genomic biomarker research promises to provide more precise predictors of outcome to treatment not previously attainable with traditional biomarkers. However, before genomic biomarker tests become commonplace in clinical practice, several issues need to be addressed in order to generate the essential levels of evidence to demonstrate analytical and clinical validity and utility. Assay validation is required not only in the context of in-house developed assays (i.e. “homebrew” tests) but also prior to the use of commercially available Food and Drug Administration (FDA)-approved diagnostic tests. This presentation will illustrate some the steps required to achieve clinical utility of a diagnostic test.
2:30-3:00 Molecular Diagnostics Laboratories (MoDEL): A Program to Support Cancer Biomarker Clinical Assay Development
J. Milburn Jessup, M.D., Chief, Diagnostics Evaluation Branch, Cancer Diagnosis Program, DCTD/National Cancer Institute
Although Biomarkers will become increasingly important as targeted and personalized therapies dominate the care of the cancer patient, the development and validation of useful biomarkers is often stopped by inadequate assay development. The Cancer Diagnosis Program (CDP) of NCI issued a Request for Information that defined significant needs for assay development as: specimen acquisition, access to standards and reagents, guidance on assay development for academia to facilitate transfer to industry, and support for improving assay performance, evaluation and validation for clinical use. As a result, CDP will present its plans for developing MoDEL as a suite of services that 1) will assist the utilization of Biomarkers in late phase clinical trials in oncology and 2) will be available to both academia and industry.
3:00-3:30 Networking Refreshment Break
CLOSING PLENARY SESSION:
CIRCULATING TUMOR CELLS
(Shared session with Biomarker Assay Development meeting)
3:30-4:00 Circulating Tumor Cell Assays: A Prognostic and Predictive Factor for Breast, Prostate and Colon Cancer
Herbert A. Fritsche, Ph.D., Professor and Chief, Clinical Chemistry, The University of Texas M. D. Anderson Cancer Center
The current hypothesis of cancer metastasis proposes that tumor cells escape into the blood and circulate until they are either eliminated by host response mechanisms or until they find an environment in which to reside in a dormant condition and to proliferate at a later time. Thus, the detection of circulating tumor cells may represent an early indication of micro-metastasis or of aggressive tumors which are able to shed tumor cells into the blood. The circulating tumor cells can be captured using antibody labeled magnetic beads, either in positive or negative selection schema. After the circulating tumor cells are isolated, they may be characterized by immunohistochemistry and counted. Alternatively, these cells may be characterized by gene expression analysis using RT-PCR. One of the CTC detection methods (Veridex Inc, Cell Search Assay) has been cleared by the US FDA for use as a prognostic test in patients with metastatic cancers of the breast, prostate and colon. In these cases of metastatic cancer, the pre-treatment presence of tumor cells is prognostic of a poor outcome, at any time during the course of the disease. Furthermore, in metastatic breast cancer patients, the presence of tumor cells at the end of the first course of chemotherapy is predictive of treatment failure. Thus, the CTC test may permit the oncologist to make an early decision to discontinue first line therapy for metastatic breast cancer and pursue more aggressive alternative treatments. We have addressed the practical aspects of routine testing for CTC’s using the Veridex Cell Search method. We have also evaluated the Adnagen Breast Cancer Cell Select and Detect assay for CTC detection. The method uses multi-antigen cell capture with antibody labeled magnetic beads, followed by RT-PCR characterization of selected genes. This assay may compliment the Cell Search assay for tumor cell detection in blood. Other CTC assays based on new capture technologies are currently in development.
4:00-4:30 Biomarker Assay Development and Validation: An Epiphany for Drug Development and the Management of Patients with Cancer
Martin Fleisher, Ph.D., Chair, Dept. of Clinical Laboratories, Memorial Sloan-Kettering Cancer Center
Biomarkers can be used to predict whether or not a treatment modality is effective in early-stage clinical trials, judge the response to therapy, identify which cancer patients are at high risk of tumor recurrence and predict how effective an investigational drug is against a specific type of cancer. This information is valuable when decisions must be made on stratifying patients based on likely response to the therapy. We have initiated a biomarkers development and validation program that focuses on targeted therapy in patients with prostate and ovarian cancer and mesothelioma. The enumeration of circulating tumor cells (CTC) in patients with metastatic prostate cancer (PC) receiving targeted therapy for androgen receptor over expression has demonstrated impressive clinical sensitivity when compared with PSA response. As new targeted therapies enter the pipeline, predicting the effectiveness of the drug on the target by isolating and characterizing CTC in patients with metastatic cancer is clinically essential. In patients with ovarian cancer, biomarkers validated in our laboratory, such as YKL-40, HE4 and Mesothelin have been shown to be more effective than CA125 in monitoring Stage 1 and 2 ovarian disease and in detecting tumors with mucinous histology. Two biomarkers, Osteopontin and Mesothelin, have been validated and measured in patients with mesothelioma before and after chemo- and radiation therapy. Preliminary data suggest that these two biomarkers will be clinically effective in staging patients for future therapy and in monitoring recurrence of disease. Our CLIA certified laboratory has developed a rigorous validation protocol that assesses the pre- analytical, analytical and post-analytical assay performance characteristics of biomarkers under clinical evaluation. This validation protocol optimizes biomarker effectiveness essential for pharmacodynamic and clinical outcome studies.
4:30 Close of Conference