Cambridge Healthtech Institute’s Third Annual
Clinical Application of Cell-Free DNA
Ensuring Clinical Value of Non-Invasive Diagnostics
August 24-25, 2016 | Grand Hyatt Washington | Washington, DC
The quest for validation of circulating cell-free DNA for monitoring treatment response, managing drug resistance and enabling early diagnosis has led to the rapid rise of this industry and importance in the medical community. The use of circulating cell-free DNA to replace tissue biopsy in solid cancers is controversial, but it is clear that it will be an essential tool for monitoring disease in blood borne cancers. The field of maternal and fetal medicine has been greatly advanced by the use of circulating fetal DNA, and will provide lessons for the oncology field for clinical and analytical validation and facing regulatory hurdles.
Day 1 | Day 2 | Short Courses | Download Brochure
SC3: Translating CTCs for Clinical Use
SC5: Establishing the Value of Diagnostic Tests
*Separate registration required
WEDNESDAY, AUGUST 24
10:30 am Registration
11:15 PLENARY KEYNOTE SESSION: Click here for details
12:40 pm Luncheon Presentation to be Announced
1:25 Ice Cream and Cookie Break in the Exhibit Hall with Poster Viewing
1:50 Chairperson’s Opening Remarks
Maximilian Diehn, M.D., Ph.D., Assistant Professor, Radiation Oncology, Stanford Cancer Institute, Institute for Stem Cell Biology & Regenerative Medicine, Stanford University
2:00 KEYNOTE PRESENTATION: A Regulatory Perspective on Tumor Gene Panels
Eunice Lee, Ph.D., Chief, Office of In Vitro Diagnostics and Radiological Health, Center for Devices and Radiological Health, US Food and Drug Administration
High throughput assays are rapidly being employed for oncology applications in the clinical setting. This has introduced new challenges to the regulatory paradigm for in vitro diagnostic devices (IVDs). An overview of the regulatory landscape for IVDs will be provided, including companion and complementary diagnostics. The complexities associated with tumor gene panels intended to evaluate liquid biopsies will also be discussed, highlighting considerations for validating the performance of the assays.
2:30 Multipanel Massive Parallel Sequencing cfDNA in Monitoring Cutaneous Melanoma Progression
David S. B. Hoon, Ph.D., MSc, Chief of Scientific Intelligence; Director, Molecular Oncology; Director, JWCI Sequencing Center, John Wayne Cancer Institute
Analysis of cfDNA gene mutation panel in melanoma patients serial bleeds over several years of follow-up can be very informative on events ongoing during tumor progression. The highly sensitive and approach of multiple gene mutation panel assessment by MPS of cfDNA provides a very comprehensive analysis to allow correlation to real-time clinical events of patients. These retrospective studies demonstrate that cfDNA mutations can arise at different time points during tumor progression. This approach of precision medicine monitoring melanoma progression allows a more accurate real-time assessment of what is transpiring in the patient.
3:00 Dynamic Changes in Circulating Tumor DNA in Urine after Drug Administration
Hatim Husain, M.D., Physician, Medical Oncology, University of California, San Diego
We have been able to monitor early drug response to anti-EGFR therapy to model tumor lysis. We will be presenting data on pretreatment kinetics and dynamic changes in ctDNA for patients across anti-EGFR therapies and other genotypes in lung cancer. The data presented will be evaluating urine as a modality for monitoring ctDNA.
3:30 Multiplexed ICE COLD PCR Enriches Any Low-Level Mutation Present in DNA Isolated from FFPE and Plasma Samples
Ben Legendre, Jr., Vice President, Laboratory Operations, Transgenomic, Inc.
Using Multiplexed ICE COLD-PCR, cancer patients’ DNA isolated from FFPE & Plasma was utilized to enrich for any low level mutations present in the samples. The results demonstrated detection of low level mutations in liquid biopsies; thus allowing for disease management with respect to treatment options and/or drug cocktail modifications for cancer patients.
4:00 Refreshment Break in the Exhibit Hall with Poster Viewing
4:40 Chairperson’s Opening Remarks
Luis A. Diaz, M.D., Associate Professor, Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Conference Chairman
4:45 Analysis of cfDNA to Monitor Metastatic CRC Patients and Manage Drug Resistance
Scott Kopetz, M.D., Ph.D., FACP, Associate Professor, Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center
Circulating cell-free DNA provides an opportunity for rapid interrogation of patient responses for metastatic colorectal cancer patients. Mechanisms of resistance and heterogeneity can also be interrogated with this methodology. This lecture will provide illustrative cases and discussion of the opportunities and hurdles for implementation.
5:15 Liquid Biopsy Approaches for Characterizing Cancer Genomes
Victor Velculescu, M.D., Ph.D., Professor, Oncology; Co-Director, Cancer Biology, Johns Hopkins Sidney Kimmel Cancer Center; Co-Founder, Personal Genome Diagnostics
Analyses of cancer genomes have revealed mechanisms underlying tumorigenesis and new avenues for therapeutic intervention. In this presentation, I will discuss lessons learned through the characterization of cancer genome landscapes, challenges in translating these analyses to the clinic, and new technologies that have emerged to analyze molecular alterations in the circulation of cancer patients as cell-free tumor DNA. These approaches have important implications for non-invasive detection and monitoring of human cancer, therapeutic stratification, and identification of mechanisms of resistance to targeted therapies.
5:45 Evaluation of Circulating DNA Analysis in Oncology: Multi-Center Clinical Trials in Europe and Efforts to Standardize Collection of Material and Interpretation of Results
Alain R. Thierry, M.D., Director, Research, Research Institute in Oncology of Montpellier, INSERM
Following critical observations in the past 10 years, numerous studies of clinical validation and clinical utility of circulating DNA analysis, especially in oncology, are ongoing. However, no consensus is made in the field toward setting guidelines and better Standard Operating Procedures (SOP). A comprehensive set of rigid criteria outlining the blood collection, handling, plasma preparation, cirDNA extraction and storage conditions are needed. We will discuss our experience in leading various multicenter, prospective, blinded assays.
6:15 Close of Day
6:00 Dinner Short Course Registration
6:30-8:30 RECOMMENDED DINNER SHORT COURSE*
SC14: Liquid Biopsy: Clinical Applications and Business Considerations
*Separate registration required
Day 1 | Day 2 | Short Courses | Download Brochure
THURSDAY, AUGUST 25
7:30 am Problem-Solving Breakout Discussions with Continental Breakfast
8:25 Chairperson’s Opening Remarks
David S. B. Hoon, Ph.D., MSc, Chief of Scientific Intelligence, Director, Molecular Oncology, Director, JWCI Sequencing Center, John Wayne Cancer Institute
8:30 Clinical Applications of Tracking Plasma AR Aberrations in Castration-Resistant Prostate Cancer
Daniel Wetterskog, Ph.D., Senior Scientific Officer, Centre for Evolution and Cancer, Translational Biology of Urological Cancers Team, Institute of Cancer Research
Our group has been using plasma to interrogate resistance in castration-resistant prostate cancer (CRPC) and develop biomarkers for selecting treatment. Using targeted next-generation sequencing of cfDNA from sequential plasma samples we identified AR mutations emerging with resistance to abiraterone. We also identified a strong association between plasma AR aberrations and resistance to abiraterone in heavily-pretreated CRPC patients. Our data support the clinical utility of cfDNA studies in metastatic prostate cancer.
9:00 Genomic Alterations in Cell-Free DNA and Enzalutamide Resistance in Castration-Resistant Prostate Cancer
Alexander W. Wyatt, Ph.D., Senior Research Scientist, Vancouver Prostate Centre, Assistant Professor, University of British Columbia
The molecular landscape underpinning response to the androgen receptor (AR) antagonist enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) patients is undefined. We collected temporal cfDNA samples from 65 mCRPC patients receiving enzalutamide and performed deep sequencing. AR amplification was associated with primary resistance, as was heavily mutated AR. AR mutations exhibited clonal selection during treatment. At progression cfDNA sequencing revealed mutations or copy number changes in all patients tested, including clinically-actionable alterations in DNA damage repair genes and PI3K pathway genes.
9:30 Presentation to be Announced
10:00 Coffee Break in the Exhibit Hallwith Poster Viewing
10:50 Characterizing Clonal Evolution and Treatment Resistance Using Circulating Tumor DNA Analysis
Muhammed Murtaza, Ph.D., MBBS. Assistant Professor and Co-Director, Center for Noninvasive Diagnostics, Translational Genomics Research Institute
Analysis of circulating tumor DNA is moving rapidly towards clinical applications such as noninvasive tumor genotyping, monitoring of tumor burden and tracking clonal evolution. However, there is little evidence evaluating the extent of tumor heterogeneity that can be captured in plasma DNA. In this presentation, I will share insights gained from extensive comparison between multi-regional tumor biopsies and serial plasma samples in a patient with breast cancer.
11:20 Circulating Cell-Free DNA: A Novel Gateway to the Genome of Hodgkin/Reed-Sternberg Cells in Hodgkin’s Lymphoma?
Peter Vandenberghe, M.D., Ph.D., Head, Laboratory for the Cytogenetic and Molecular Diagnosis of Malignant Diseases, Center for Human Genetics, University Hospitals Leuven; Professor, Medicine, Human Genetics, KU Leuven
Non-invasive massive parallel sequencing of ccfDNA allows the identification of genomic imbalances in Hodgkin/Reed-Sternberg (HRS) cells in early and advanced stage classical Hodgkin’s lymphoma (cHL). Given the scarcity of HRS cells in cHL biopsies, this observation opens important new perspectives for genetic investigation of cHL, and may facilitate the development of targeted and precision therapy in cHL.
11:50 Monitoring of Circulating Tumor DNA in Diffuse Large B-Cell Lymphoma
Mark Roschewski, M.D., Staff Clinician, Commissioned Corps, United States Public Health Service, Center for Cancer Research, Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health
Monitoring treatment response in diffuse large B-cell lymphoma (DLBCL) relies on imaging scans that do not improve survival. Cell-free circulating tumor DNA (ctDNA) can be detected in patients with DLBCL. Next-generation sequencing (NGS)-based assays of ctDNA provide biologic information previously inaccessible and predict early treatment failure and disease relapse prior to CT scans in DLBCL. Will discuss clinical and research applications of ctDNA monitoring in DLBCL.
12:20 pm Liquid Biopsy: Providing Answers that Matter
Veena Singh, Medical Director, Biocept
Liquid biopsies offer the opportunity to interrogate a number of different target sample types, including ctDNA and CTCs. At Biocept both ctDNA and CTCs are used for identifying medically actionable biomarkers to assist in the optimal treatment of patients. Learn more about biomarkers on blood and providing answers that matter.
12:50 Luncheon Presentation to be Announced
1:20 Session Break
1:35 Presentation to be Announced
2:00 Moderator’s Remarks
John Beeler, Ph.D., Vice President, Business Development, Inivata
- How much content is valuable? How many genes are necessary or ideal in a gene panel?
- What are oncologists and patients looking for?
- How are Doctors using data to make decision?
- What is the ideal technology to use? Do you need a comprehensive panel upfront? Discussion of technology and utilization
- How does cost factor in?
- How does regulatory approval factor in?
Regulation: Abraham Tzou, M.D., Medical Officer, FDA
CLIA New York State: Stephanie Shulman, M.P.H., M.S., M.T. (ASCP), Director, Clinical Laboratory Evaluation Program, Wadsworth Center, New York State Department of Health
Policy: Sean Tunis, CEO, Center for Medical Technology Policy
Oncologist: Liquid Biopsy: Use in Clinical Trials
Barbara A. Conley, M.D., Associate Director, Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute (tentative)
Liquid biopsies offer the promise of interrogating a patient’s cancer without a biopsy, as well as being able to longitudinally sample the molecular profile. Potential uses for “liquid biopsy” in clinical trials include initial diagnosis, target-finding (predictive marker), pharmacodynamics assays and ascertaining development of resistance. Qualities of a fit for purpose liquid biopsy for use in clinical trials for cancer drug development will be presented.
Payer: Elaine Jeter, M.D., Contractor & Medical Director, Palmetto GBA LLC
Investor: Eli Casdin, Managing Member, Casdin Capital
4:05 Close of Conference
Day 1 | Day 2 | Short Courses | Download Brochure