Cambridge Healthtech Institute’s Inaugural

Genomic Technologies for Patient Stratification

Unlocking New Markers to Ensure Successful Treatment

February 16-18, 2015 | Moscone North Convention Center | San Francisco, CA
Part of the 22nd Annual Molecular Medicine Tri-Conference

 

Early patient stratification is critical to enable effective and personalized drug discovery and development. Genomic Technologies for Patient Stratification will showcase novel technologies and techniques that are being used by researchers to stratify patient populations into an appropriate trial. Emphasis will be placed on identifying and generating new biomarker leads to maximize the chances of successful treatment. The importance of high-speed and accurate methods for marker detection will also be examined, and case studies using new techniques and technologies to take advantage of a patient's genotype will be showcased. Attendees will come away with the knowledge and tools to move forward in the rapidly advancing area of personalized medicine.


Day 1 | Day 2 | Day 3 | Plenary Session | Download Brochure 

Monday, February 16

10:30 am Conference Program Registration


NGS-DRIVEN STRATIFIED CANCER TRIALS

11:50 Chairperson’s Opening Remarks

Steffan N. Ho, M.D., Ph.D., Senior Director, Early Development and Translational Oncology, Pfizer Oncology

12:00 pm LungMAP/S1400: A Unique Public-Private Master Protocol for Drug-Biomarker Registration

David Gandara, M.D., Professor of Medicine, Division of Hematology/Oncology, University of California, Davis School of Medicine; Director, Thoracic Oncology Program, Senior Advisor to the Director, UC Davis Comprehensive Cancer Center; Chair, Lung Committee, Southwest Oncology Group (SWOG)

Despite rapid advances in deciphering the complex genomics of non-small cell lung cancer (NSCLC), clinical translation into approvable biomarker-drug combinations has been problematic, due in part to the relative rarity of genomically-defined subsets. Lung-MAP (S1400) is a one-of-a-kind public-private partnership designed to speed up development of targeted therapies for NSCLC of squamous cell histology (SCCA). Here we describe development of this registration-compliant biomarker-driven Phase II/III multi-arm “master” protocol, employing next generation sequencing to identify actionable molecular abnormalities, followed by patient randomization to biomarker-driven targeted therapy versus standard of care.

12:30 The Evolving Genotype-to-Phenotype Paradigm in Oncology Drug Development

Steffan N. Ho, M.D., Ph.D., Senior Director, Early Development and Translational Oncology, Pfizer Oncology

The clinical application of multiplexed molecular profiling technologies offers unprecedented opportunities to enhance the drug development process by directing treatment to patients who are more likely to benefit. However, molecular profiling technologies are in the early stages of clinical application as companion diagnostic tests. Future success will require close integration between not only biology and technology, but also between clinical and diagnostic development strategies.

1:00 Enjoy Lunch on Your Own

2:30 Chairperson’s Remarks

2:40 Clinical Trials for Predictive Biomarker Discovery and Validation in Oncology Drug Development

Eric Peters, Ph.D., Companion Diagnostics Leader, Oncology Biomarker Development, Genentech 

3:10 Universal Testing for Actionable Genomic Variants in Cancer: a Paradigm Shift in Precision Oncology

Karen A. Gutekunst, Ph.D., Vice President, Diagnostic Development, Illumina, Inc.

Rapid technological progress allowing for broad interrogation of genomic variation in cancer, and a parallel expansion in knowledge regarding the actionability of an ever-growing number of germline and somatic variants, are revolutionizing the management of the disease. A paradigm shift is currently under way from drug-centered to patient-centered precision oncology, enabled by the advent of high-throughput, widely accessible NGS-based “universal” cancer genomic testing and featuring the emergence of “companion therapeutics”.

3:40 PANEL DISCUSSION: Challenges in Developing Oncology Therapy with the Complexity of Cancer Heterogeneity

Panel Moderator: Steffan N. Ho, M.D., Ph.D., Senior Director, Early Development and Translational Oncology, Pfizer Oncology

Panelists: David Gandara, M.D., Professor of Medicine, Division of Hematology/Oncology, University of California, Davis School of Medicine; Director, Thoracic Oncology Program, Senior Advisor to the Director, UC Davis Comprehensive Cancer Center; Chair, Lung Committee, Southwest Oncology Group (SWOG)

Eric Peters, Ph.D., Companion Diagnostics Leader, Oncology Biomarker Development, Genentech

Karen A. Gutekunst, Ph.D., Vice President, Diagnostic Development, Illumina, Inc.

 

SpeeDx4:10 Evolving Clones and Detection Technology: Role in Cancer Management

Alison Todd, Ph.D., CSO and General Manager, SpeeDx Pty Ltd

The growing need to understand tumor heterogeneity and clonal evolution, and their potential significance for tailoring and monitoring therapy, reinforces the necessity for highly sensitive, rapid and accurate analytical tools.   This presentation will outline novel approaches useful for clinical implementation.

4:40 Break and Transition to Plenary Session

5:00 Plenary Session 

6:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing

7:30 Close of Day


Day 1 | Day 2 | Day 3 | Plenary Session | Download Brochure 

Tuesday, February 17

7:00 am Registration and Morning Coffee

8:00 Plenary Session 

9:00 Refreshment Break in the Exhibit Hall with Poster Viewing


RNA SEQ FOR PATIENT STRATIFICATIOn

10:05 Chairperson’s Remarks

10:15 Genetic Profiling of Hematologic Malignancies

Omar Abdel-Wahab, M.D., Assistant Member, Human Oncology and Pathogenesis Program and Leukemia Service, Medicine, Memorial Sloan Kettering Cancer Center

Clinical, cytogenetic, and gene-based studies have been used to inform biology and improve prognostication for acute myeloid leukemia (AML) patients. We and others have shown somatic mutations can be used to improve risk stratification in AML. We have more recently worked to develop assays for genomic profiling of leukemia, lymphoma and myeloma patients and demonstrated how these assays can be used to inform clinical care.

10:45 Sequencing Approaches for Personalized Cancer Therapy Selection and Monitoring

Daniela Starcevic, Ph.D., Director, Diagnostic Sequencing; Assistant Professor, Genomics and Multiscale Biology; Assistant Professor, Pathology; Icahn School of Medicine at Mount Sinai

The Personalized Cancer Therapy program is aimed at developing molecular diagnostics for better disease management: therapy selection and monitoring. Patients’ samples undergo state of the art sequencing and bioinformatics towards molecular level understanding of disease and a comprehensive/integrated approach for finding alternate, innovative and more effective treatment options. The opportunities and challenges of sequencing and analyzing tumor samples will be addressed and illustrated with examples.

11:15 Precision Oncology through Genomic Testing Strategies and Clinical Trials

Sameek Roychowdhury, M.D., Ph.D., Assistant Professor, Internal Medicine, Ohio State University Comprehensive Cancer Center

Dr. Roychowdhury will present on evolving use of genomic testing strategies for clinical decision making and eligibility, followed by challenges and approaches for application in clinical trials.

11:45 Accelerating the Velocity of Therapeutic Approval and Adoption

Kathryn Becker, Ph.D., Director, Global Marketing, CDx, Abbott Molecular

Abbott employs a variety of partnership models that support pre-clinical biomarker studies, complete development, indication expansion, and commercialization of CDx products.  One core competency employed in all partnerships is the ability to simplify complex technologies, like multiplex molecular analysis, to enable adoption within the local clinical communities and support reproducible, reliable results on a global scale

12:15 pm Session Break

12:25 Luncheon Presentation: Innovative Targeted RNA-Seq Method for Identifying Known and Novel Gene Fusion Events in Tumor Cells

Jonathan Scolnick, Ph.D., Scientist, Research, NuGEN Technologies

The novel Single Primer Enrichment Technology (SPET) and how it differs from existing target enrichment methods will be described. Sensitive variant detection from genomic DNA derived from fresh and FFPE tissues using 344 cancer-related genes will be demonstrated as well as utilization of SPET as a rapid, cost-effective screening tool for discovery of novel fusions and detection of known fusions with a panel of 500 cancer genes implicated in fusions events.

12:55 Session Break

1:25 Refreshment Break in the Exhibit Hall with Poster Viewing


PCR FOR PATIENT STRATIFICATION

2:00 Chairperson’s Remarks

Andrew Brooks, Ph.D., COO, RUCDR Infinite Biologics; Associate Professor, Genetics, Rutgers University

2:10 Digital PCR for Patient Monitoring and Stratification in Clinical Trials

Reinhold Pollner, Ph.D., Director, Clinical Trial Assay Development, Genoptix Medical Laboratory, a Novartis Company

My presentation will focus on how digital PCR is used in the validation of clinical trial assays with respect to patient monitoring and stratification in a CLIA/CAP laboratory setting. A variety of different applications of digital PCR will be discussed ranging from the determination of DNA copy numbers in FFPE samples, absolute quantitation of a transgene in whole blood and bone marrow samples, identification of a fusion gene at the mRNA level in FFPE specimens, and rare allele detection using circulating tumor DNA.

2:40 Evaluation of EGFR Mutations in Plasma from NSCLC Patients: Utility in Managing Patients on TKI Therapy

Chris Karlovich, Ph.D., Principal Scientist, Molecular Diagnostics, Clovis Oncology

We are utilizing blood-based molecular testing in patients who have become resistant to first generation tyrosine kinase inhibitors with the goal of enabling subsequent therapy without need for repeat lung biopsy. The utility of plasma-based EGFR mutational analysis will be described in the context of CO-1686, a novel third-generation TKI that selectively inhibits the EGFR activating and T790M resistance mutations in NSCLC patients.

3:10 NGS-Assisted DNA-Based Digital PCR for the Detection and Quantification of Residual Disease in CML Patients with Undetectable BCR-ABL1 Transcripts

Mary Alikian, MSc, Clinical Scientist, Imperial Molecular Pathology, Imperial College

The presentation will describe a DNA-based method of detecting and quantifying low levels of BCR-ABL1 positive disease that improves on previous methodologies in two key areas: Identifying the patient-specific genomic BCR-ABL1 fusion junctions using targeted next generation sequencing allowing the rapid generation of high-performing DNA based qPCR assays. The second area is: Use of a DNA-based approach by optimizing the technique for use on a digital PCR (dPCR) platform, which provides absolute molecular quantification without the need for standard curve.

3:40 Precision Molecular Profiling of Cancer using ddPCR

Jennifer Berman, Ph.D., Staff Scientist, Digital Biology Center, Bio-Rad Laboratories

Cutting-edge, personalized cancer care requires ultra-sensitive detection and monitoring of actionable mutations from limited patient samples. The high sensitivity and precision of droplet digital PCR (ddPCR) offers critical advantages when clinical samples are limiting, degraded, and contain PCR inhibitors. We highlight use of ddPCR for quantification of KRAS mutations in FFPE and plasma cfDNA, as well as detection of copy number alterations of oncogenes like MYC, HER2, and EGF

4:10 Mardi Gras Celebration in the Exhibit Hall with Poster Viewing

5:00 Breakout Discussions in the Exhibit Hall

How to Overcome the Hurdles towards More Efficient Pharma – Academia Collaborations

Moderator: Daniela Starcevic, Ph.D., Director, Diagnostic Sequencing; Assistant Professor, Genomics and Multiscale Biology; Assistant Professor, Pathology; Icahn School of Medicine at Mount Sinai

  • Overcoming the hurdles towards a more expedient translation of research findings from the bench to the clinic
  • Understanding cultural and operational differences in pharma and academia
  • Types of collaborations that maximize chances of success for both sides
  • Structuring agreements towards successful outcomes

Implementation Strategies for NGS-Based Companion Diagnostics

Moderator: John D. Pfeifer, M.D., Ph.D., Vice Chairman for Clinical Affairs and Professor, Pathology and Immunology; Professor, Obstetrics and Gynecology, Washington University School of Medicine

  • Issues related to the fact that different genes have targeted therapies from different Pharma companies
  • Issues related to the fact that different NGS platforms have different test metrics
  • Issues related to the fact that different NGS test designs identify different classes of mutations

Pathology Support for Master Protocol Development and Implementation

Moderator: Philip C. Mack, Ph.D., Associate Adjunct Professor, Internal Medicine, Hematology and Oncology, University of California Davis Medical Center

  • Need and Rationale for a Master Protocol Clinical Trial Design
  • Requirements and Challenges for Optimal Specimen Submission and Analysis
  • Future Steps for Master Protocol Innovation

6:00 Close of Day


Day 1 | Day 2 | Day 3 | Plenary Session | Download Brochure 

Wednesday, February 18

7:00 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

8:00 Plenary Session Panel 

9:45 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall


PATIENT RECRUITMENT USING BIOMARKER ANALYSIS TOOLS

10:35 Chairperson’s Remarks

Jaya Goyal, Ph.D., Director, Value Based Medicine, Biogen Idec

10:45 Demonstration of the Utility of Point-of-Care Genotyping Technologies to Actively Recruit into Genotype Stratified Studies

Charles Cox, Ph.D., Head, Genetics Experiment Design and Delivery, GlaxoSmithKline

We describe the design of an innovative experimental medicine study to assess the impact of a variant in the OPRM1 gene on a novel mu opioid receptor antagonist, with recruitment stratified by genotype. This study highlights the challenges of recruitment of individuals from Biobanks, and how we were able to rapidly design and test point of care genotype assays from 3 manufactures and use them to successfully recruit into this study.

11:15 Survival Improvement by Personalized Genomic Diagnostics for Ovarian Cancer Chemotherapy

Jae Lee, Ph.D., Chair and Senior Member, Biostatistics and Bioinformatics, Moffitt Cancer Center

We have developed co-expression extrapolation (COXEN) biomarker models for simultaneously predicting patient response to three standard chemotherapy drugs used to treat advanced EOC: paclitaxel, cyclophosphamide, and topotecan. Our study has retrospectively, yet independently, showed a potential for genomic biomarker-based personalized chemotherapy selection to significantly improve survival of patients in the heterogeneous EOC population when using standard chemotherapies.

11:45 Epigenetic Profiling in Endometriosis Laser Capture Microdissection Enables Targeted Analyses

Eva Simon, Ph.D., Gynecological Therapies, Bayer HealthCare AG

By optimizing the NuGEN Ovation® Ultralow Methyl-Seq Library protocol we succeeded in producing RRBS libraries from less than 10 ng DNA, isolated from human tissue slices. The systematic analysis of epigenetic changes in separated cell populations of eutopic, ectopic and normal endometrium is expected to improve our knowledge about the pathogenesis of endometriosis. Results may contribute to the development of more effective treatment strategies as well as to the identification of new therapeutic targets and reliable biomarkers for early stage diagnosis in endometriosis.

12:15 pm Enjoy Lunch on Your Own

1:00 Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing


LOOKING BEYOND THE DIRECT MOLECULAR TARGETS OF DRUGS

1:40 Chairperson’s Remarks

Ken Chang, Ph.D., Senior Principal Scientist, Molecular Biomarkers and Diagnostics, Merck Clinical Labs

1:50 Molecular and Clinical Predictors of Disease Status, Trajectory and Treatment Response Enabling Patient Stratification

Jaya Goyal, Ph.D., Director, Value Based Medicine, Biogen Idec

Identification of subgroups of patients with shared disease characteristics by using a combination of molecular, clinical, biochemical and imaging testing to select the optimal therapy for individual patient will result in optimal treatment outcome. Approaches for the post-hoc analysis of clinical trial data and samples to identify baseline clinical, radiographic and molecular variables associated with disease status, disease trajectory and outcome will be presented.

2:20 Contextualization of Individualized Patient Molecular Profiles Enabling Patient Stratification and Association with Distinct Clinical Characteristics

Ahmed Enayetallah, M.D., Ph.D., Senior Scientist, Value Based Medicine, Biogen Idec

Post-hoc analysis of molecular data collected from two large phase III clinical trial data to identify and characterize disease heterogeneity with the goal of uncovering patient subpopulations that are defined by their active molecular signals. Individualized patient molecular profiling and contextualization of observed molecular changes enabled molecularly-defined patient stratification and revealed subpopulations associated with distinct clinical characteristics. The analysis also characterized the molecular mechanisms potentially driving the clinical characteristics.

2:50 Orion Bionetworks, a Novel Cooperative Partnership for Systems Modeling and Biomarker Discovery for Brain Diseases

Magali Haas, M.D., Ph.D., Founder and CEO, Orion Bionetworks

This talk will describe a new Cooperative Alliance founded to accelerate time to cure for brain disorders by harnessing the power of big data and predictive analytics to build systems models of brain diseases, starting with multiple sclerosis and prodromal schizophrenia. Specifically, we will describe the development of prognostic diagnostic tools for multiple sclerosis and other neurodegenerative disorders through the application of high performance computing and predictive analytics on phenotypic, biosensor, clinical and biomarker data.

3:20 Genomic Predictors for Two Distinct Recurrence Patterns of Hepatocellular Carcinoma

Ju-Seog Lee, Ph.D., Associate Professor, Systems Biology, Division of Cancer Medicine, UT MD Anderson Cancer Center

Typically observed at 2 years after surgical resection and distinct from early recurrence, late recurrence is a major challenge in the management of hepatocellular carcinoma (HCC). Current prognostic models cannot discriminate between late and early recurrence, and clinically relevant biomarkers for either type have not been established. Systematic analysis of gene expression data from human liver undergoing hepatic injury and regeneration (HIR) revealed the signature that was significantly associated with late recurrence of HCC. By using HIR signature, we developed a prognostic predictor that can identify patients at high risk of late recurrence and the robustness of the predictor was tested and validated in three independent cohorts (n=396 patients). In multivariate analysis, this signature was the most significant risk factor for late recurrence (hazard ratio, 2.2; 95% confidence interval, 1.3–3.7; P = 0.002). In contrast, previously developed tumor-derived 65-gene risk score was significantly associated with early recurrence (P = 0.005) but not with late recurrence (P = 0.7). In multivariate analysis, the 65-gene risk score was the most significant risk factor for very early recurrence (<1 year after surgical resection) (hazard ratio, 1.7; 95% confidence interval, 1.1-2.6; P = 0.01). Gene network analysis revealed NOTCH1 and STAT3 might play important roles in late recurrence. Conclusion: Two independently developed predictors — 65-gene risk score and HIR signature — reflect well the biological differences between early and late recurrence of HCC and provide new biomarkers for risk stratification. 

3:50 Refreshment Break


UNLOCKING NEW MARKERS FOR STRATIFICATION

4:00 Chairperson’s Remarks

Jae Lee, Ph.D., Chair and Senior Member, Biostatistics and Bioinformatics, Moffitt Cancer Center

4:10 Identifying and Overcoming Markers of Chemoresistance

Jason Baum, Ph.D., Associate Director, Companion Diagnostics, Research, Merrimack Pharmaceuticals

This talk will focus on the understanding of cancer cell survival networks to identify key biomarkers of resistance to chemotherapy. This includes initial proof-of-concept in a pre-clinical setting and translation into the clinic through the development of both tissue and blood-based diagnostic assays. Data from phase II clinical studies will illustrate the resistance of biomarker positive patients to chemotherapies across multiple indications, and the potential for targeted therapies to overcome this resistance.

4:40 The Impact of Tumor Heterogeneity on Clinical Biomarker Development using FFPE Tissue

Ken Chang, Ph.D., Senior Principal Scientist, Molecular Biomarkers and Diagnostics, Merck Clinical Labs

We have developed a “Concordance Calculator” to quantify reproducibility of multi-variant calls among Next Generation Sequencing replicates. This novel approach also allowed us to eliminate many different technical artifacts including Post Tissue Collection Modifications such as deamination and oxidation artifacts. Our most recent studies suggest that DNA mutation signatures as novel biomarkers for cancer diagnosis and prognosis are likely to be less sensitive to the impact of tumor heterogeneity than RNA-based expression signatures.

5:10 Prognostic Surrogate Markers for Survival, A Case Series for a Novel Antiangiogenic Therapy

M.A. Nezami, M.D., President, Cancer Epigenetics, Pacific Medical Center of Hope

Establishing the prognosis in majority of patients, especially with heterogeneous tumors, has been extremely challenging. One area of most recent attention in identifying surrogate markers for survival has been the vasculogenesis and its related serum markers. Here we present a series of cases treated with a novel antiangiogenic therapy and monitored through these markers to identify response that translated to prognosis and survival.

5:40 Close of Conference Program



Day 1 | Day 2 | Day 3 | Plenary Session | Download Brochure 

Premier Sponsors:   

Elsevier    

Jackson Laboratory - small logo  

 NanoString2    

 Precision for Medicine 

SeraCare 

Silicon Biosystems 

Thomson Reuters-Large