Drug discovery is a long, costly process with a high attrition rate, and a personalized medicine strategy is needed to improve clinical outcomes. Identifying the subclass of patients who is likely to respond to drugs and developing biomarkers for patient stratification before recruitment for clinical trials would improve efficacy and response rates. Cambridge Healthtech Institute’s Fifth Annual Biomarkers for Patient Selection meeting will explore the integration of biomarkers and companion diagnostics into drug development, case studies of using biomarkers to guide clinical decision making, molecular profiling approaches and their impact on clinical development, as well as personalized medicine initiatives at big pharma.
Final Agenda
Wednesday, May 3
12:00 pm Conference Registration
12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:30 Dessert Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Opening Remarks
Robert Iannone, M.D., Senior Vice President & Head, Immuno-Oncology, Global Medicines Development, AstraZeneca
2:05 Immunophenotyping to Differentiate Responder and Non-Responder Patients in Cancer Immunotherapy
George Poste, D.V.M., Ph.D., Chief Scientist, Complex Adaptive Systems, Arizona State University
The clinical benefits of immune checkpoint inhibitors in a variety of malignancies are unprecedented. Unfortunately, the level of positive therapeutic response is not consistent across different tumor classes and even in responsive tumor lineages non-responders still dominate. The need for comprehensive immunophenotyping to identify the mechanisms underlying these differential reponses and better predict responder patients is an urgent clinical and economic imperative.
2:30 Rational Combinations with PD-L1 Antagonists
Robert Iannone, M.D., Senior Vice President & Head, Immuno-Oncology, Global Medicines Development, AstraZeneca
2:55 Non-Clinical Approaches to Predict Single Agent vs. Combination Value and Clinical Development Strategies for Emerging Cancer Immunotherapies
James Smothers, Ph.D., Senior Director & Head, Discovery, Immuno-Oncology & Combinations DPU, GlaxoSmithKline
A rapidly growing number of immunotherapy treatments for cancer have entered clinical trials and are being evaluated for both single agent and combination therapeutic value. Currently approved or mature Phase III evaluations of immuno-oncology treatments are largely limited to strategies that employ either autologous T-cell treatments or use of monoclonal antibodies (mAbs) to block T-cell checkpoints of either activation or exhaustion. Other modalities being explored in late phase preclinical and early clinical development include agonistic mAbs that modulate healthy immune cell populations, small molecule chemistries to inhibit or drive enzymatic function, and other emerging or reconsidered approaches to experimental medicine design. Non-clinical research studies historically support preclinical development and regulatory submission satisfaction and provide critical support of early clinical development hypotheses and clinical trial design including managing expectations of single agent efficacy or setting strategic vision for combination value through biology synergies. Moreover, following early clinical development milestones, an experimental medicine requires ongoing translational review of the clinical readouts beyond efficacy which in turn requires additional non-clinical analyses and experimental execution to drive results-based decision making and data-informed design of late stage clinical trials in anticipation and hope of drug approvals. Examples of non-clinical studies to support all of these activities will be reviewed including choice of experimental models and design.
3:20 Refreshment Break in the Exhibit Hall with Poster Viewing
4:10 Chairperson’s Opening Remarks
Jeff Fill, MBA, MT (ASCP), Director, Diagnostic & Experimental Pathology, Eli Lilly and Company
4:15 From Research to CAP/CLIA to GCP – How to Make It Work!
Jeff Fill, MBA, MT (ASCP), Director, Diagnostic & Experimental Pathology, Eli Lilly and Company
It is a challenge to maintain a quality system to span from research grade assays to providing data for diagnostic submission. The Clinical Diagnostic Laboratory is utilizing a unique quality system which allows for flexibility in early biomarker discovery all the way to being a clinical trial site for diagnostic registration and all under one laboratory system.
4:40 The Application of NGS Panels for Patient Selection
Cheryl McFarlane, Ph.D., Assay Development and Validation Manager, Almac Diagnostics
NGS panels are a powerful tool for parallel assessment of genomic integrity and expression across multiple targets. This facilitates biomarker discovery in early phase clinical trials and also subsequent development of a suitable core assay for multiple drug targets. We will summarise the main considerations of development and analytical validation of such panels for patient selection and describe Almac Diagnostics’ experience identifying important technical and regulatory challenges.
5:10 Developing Robust Patient Selection Assays for Early Clinical Oncology Trials
Steven Pirie-Shepherd, Ph.D., Director, Oncology Translational Research, WRD, Pfizer
Targeted therapies are directed towards specific protein target in tumors. Tumors with the highest expression of drug targets are hypothesized to be the most likely to respond to therapy. We describe the development and analytical validation of assays intended to be used as clinical companion diagnostics to guide patient selection and stratification strategies in early stage clinical trials.
5:35 Cell-Free DNA Analysis Enabling Drug Development
Rajiv Raja, Ph.D., Director, Translational Medicine and Pharmacogenomics, MedImmune
Oncogenic mutations play an important role in patient responses to cancer therapy. Analyzing cell-free DNA (cfDNA) derived from patients can provide a robust, non-invasive method for identifying such mutations and monitoring their levels as a measure of tumor burden. Results from the evaluation of changes in variant allele frequencies in response to therapy will be presented.
5:45 Short Course and ThinkTank Registration
6:15-9:15 Dinner Executive ThinkTank*
SC6: Complementary Diagnostics
6:15-9:15 Dinner Short Course*
SC7: Immune Monitoring in Cancer
*Separate registration required
Thursday, May 4
8:30 am Morning Coffee
9:00 Chairperson’s Remarks
Johan Luthman, D.D.S., Ph.D., Vice President, Neuroscience Clinical Development, Eisai Pharmaceuticals
9:05 Precision Medicine: Why the Time Is Now!
Daniel Edelman, Ph.D., Core Manager, Clinical Molecular Profiling Core, National Cancer Institute, NIH
Once called personalized medicine, the term precision medicine has become the norm after President Obama’s support of the Precision Medicine Initiative® (PMI) in the FY 2016 budget. This new expanded research effort has the promise to create a health care system with greater efficiency of treatment and improved outcomes. In this talk we will explore multiple facets of PMI on its impact from the individual to greater health policy.
9:30 Biomarker-Supported Patient Identification Strategies for Alzheimer’s and Parkinson’s Disease
Johan Luthman, D.D.S., Ph.D., Vice President, Neuroscience Clinical Development, Eisai Pharmaceuticals
9:55 Attend concurrent session
10:20 Networking Coffee Break
10:45 Genomics and Precision Medicine: Applications in Oncology
Juliann Chmielecki, Ph.D., Associate Director, Translational Sciences, AstraZeneca
The incorporation of genomic analyses into the design of clinical trials has helped to accelerate precision medicine in oncology. Analysis of both tumor tissue and ctDNA with corresponding clinical data can help to identify mechanisms of both drug sensitivity and resistance. Examples from recent trials will be discussed. This data can then be used to identify prospective patients likely to derive maximum therapeutic benefit from targeted agents.
11:10 Large-Scale Experience with Comprehensive Clinical Genomics of Actionable Alterations in Every Patient with Advanced Cancer
Marc Ladanyi, M.D., William J. Ruane Chair in Molecular Oncology, Molecular Diagnostics Service and Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center
Through an institution-wide initiative in clinical cancer genomics initiated in 2014, we have implemented large scale genomic profiling for targetable cancer drivers and other cancer-relevant alterations in all patients with advanced solid cancers. Over 15,000 patients have been profiled using the MSK-IMPACT targeted, capture-based DNAseq assay. Subsets of patients have also been studied for oncogenic fusions by targeted RNAseq or for germline cancer predisposition alleles. An overview of our experience will be presented.
11:35 Implementing Precision Medicine into Clinical Care: Non-Small Cell Lung Cancer
David B. Roth, M.D., Ph.D., Simon Flexner Professor & Chair, Pathology and Laboratory Medicine; Director, Penn Center for Precision Medicine, Perelman School of Medicine, University of Pennsylvania
Rapid developments in targeted therapies, whose selection is driven by specific somatic mutations in a variety of genes, and in immune checkpoint blockade, whose selection is driven by expression of checkpoint receptors on the surface of tumor cells, has radically altered treatment paradigms in metastatic non-small cell lung cancer. Penn’s experience in directing appropriate, precision medicine-based therapies in this disease, involving analysis of more than 1,000 patients with routine genomic testing, will be discussed.
12:00 pm Heterogeneity and Its Effects on Patient Selection in Breast Cancer: Progress and Remaining Challenges
Christos Hatzis, Ph.D., Assistant Professor, Internal Medicine, and Director, Bioinformatics, Breast Medical Oncology, Yale University School of Medicine
Tumors expressing specific markers become eligible for treatment with targeted therapies, but only a subset of these patients respond to the treatment and have a long-term survival benefit. Identifying responding patients is complicated by the genetic heterogeneity of the tumors and its interaction with the stromal components. We will review the progress in breast cancer and outline remaining challenges.
12:25 Session Break
12:35 Luncheon Presentation: A Novel Phenotypic Platform for Predicting Tumor Response in Drug Development
Mark Paris, Ph.D., Technical Liaison, Mitra Biotech
1:40 Chairperson’s Opening Remarks
Kenna R. Mills Shaw, Ph.D., Executive Director, Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, MD Anderson Cancer Center
1:45 Building a Tool for Precision Oncology Decision Support: Getting the Right Drug(s) to the Right Patient(s) at the Right Time(s)
Kenna R. Mills Shaw, Ph.D., Executive Director, Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, MD Anderson Cancer Center
Tumor sequencing has become commonplace in cancer care. Studies reveal though that generally <10% of patients are matched to treatments using this information when outside FDA-approved indications. A resource that distills therapeutic opportunities matched to patient-specific alterations can be deployed to improve sequence data utilization. We describe how real-time notification of therapeutic opportunities and detailed functional annotations of molecular data can improve patient assignment to genomically informed clinical trials and outcome.
2:10 Overcoming Challenges in Biomarker-Associated Clinical Trials: Innovative Designs for Precision Medicine
Amir Handzel, Ph.D., Statistical Science Director, AstraZeneca
Precision medicine (PM) has emerged as a core paradigm of medical treatment, initially in oncology, now spreading to other therapeutic areas. Yet developing a predictive biomarker as companion diagnostic (CDx) is complex and requires thorough planning from early stages. PM drug development poses new challenges which have been addressed by innovative multiplexed trial designs that promise higher probability of success and efficiency. Technical aspects of the biomarkers, including threshold selection for continuous biomarkers, are critical, as demonstrated by known late-stage clinical trial failures.
2:35 Hematological Malignancy Precision Healthcare Strategies in the Therapeutic Development of Small Molecule MDM2 Antagonists
William Pierceall, Ph.D., Senior Principal Scientist, Biomarker Experimental Medicine Leader, Roche Innovation Center - New York
MDM2 antagonists block the MDM2-p53 interaction leading to stabilization and activation of p53 and tumor cell cycle arrest and apoptosis – an attractive but challenging strategy for cancer therapy. Following initial validation of this mechanism of action by nutlin-series small molecules, subsequent generation MDM2 antagonist Idasanutlin has shown notable clinical benefit in relapsed/refractory AML patients as well as patients with solid tumors. Precision healthcare strategies may provide diagnostics for identifying patients with higher likelihood of improved clinical benefit to MDM2 antagonist directed therapeutics.
3:00 Close of Conference