Cancer molecular markers provide insight and direction in overcoming tumor drug resistance, guiding therapy, determining effective immunotherapy strategies and monitoring disease progression. The Eleventh Annual Cancer Molecular Markers track will delve into the hottest areas of cancer research and determine how the latest cancer biomarkers, including cell-free DNA, circulating tumor cells, exosomes, microRNAs, extracellular vesicles, can be leveraged to greatly improve the precision of cancer therapeutics.
Monday, February 12
10:30 am Conference Program Registration Open
11:50 Chairperson’s Opening Remarks
Zhen Su, M.D., MBA, Vice President & Head of Global Medical Affairs, EMD Serono
12:00 pm KEYNOTE PRESENTATION: Predictive Biomarkers and Companion Diagnostics: The Next Wave
Ron Mazumder, Ph.D., MBA, Vice President and Global Head of Oncology, Biomarker Development and Companion Diagnostics, Genentech
I will discuss new predictive biomarkers and companion diagnostics platforms that are currently being explored or developed as companion diagnostics across our immuno-oncology, oncology and hematology programs.
12:30 KEYNOTE PRESENTATION: Precision Medicine for Immuno-Oncology: Insights into Recent Biomarker Advancements
Zhen Su, M.D., MBA, Vice President & Head of Global Medical Affairs, EMD Serono
With IO therapies rapidly evolving, the question still remains, which patients will respond? IO has changed the treatment landscape significantly, however, the respective biomarkers and diagnostics do not yet provide a clear direction for clinicians to identify the responsive patient sub-populations. From tumor associated PD-L1 expression, to T-cell infiltrates and mutational burden, we will review the current and future trends as well as discuss the challenges for IO biomarker biology.
1:00 Session Break
1:10 Luncheon Presentation I: Profiling the Changing Immune Infiltrates During Neoadjuvant Therapy For Soft-Tissue Sarcomas
Seth Pollack, MD, Assistant Member, Fred Hutchinson Cancer Research Center, Clinical Research Division; Assistant Professor, University of Washington, Division of Oncology, Fred Hutchinson Cancer Research Center
Sarcomas are a group of >70 cancers of mesenchymal origin together comprising ~1% of all cancers. Even with state-of–the-art care, >50% of patients with large, high grade tumors develop advanced disease. Immunotherapy has great potential, but little is known about the changing immune microenvironment. Using multiple approaches, including Cofactor Genomics’ Paragon assay, we have generated a molecular profile of these cancers, to better understand the changing immune TME in soft tissue sarcoma during neoadjuvant therapy.
1:40 Session Break
2:30 Chairperson’s Remarks
Robert D. Loberg, Ph.D., Executive Director of Clinical Biomarkers & Diagnostics, Amgen, Inc.
2:40 Approaches to Discovery & Development of Immuno-Oncology Biomarkers
Robert D. Loberg, Ph.D., Executive Director of Clinical Biomarkers & Diagnostics, Amgen, Inc.
The integration of a comprehensive immune-oncology biomarker and diagnostic strategy is a crucial component of the drug development process. Three key areas of focus include 1) the development of a biomarker and diagnostic strategy early, 2) enabling early biomarker efforts in pre-clinical and clinical development, and 3) the successful execution of biomarker and diagnostic driven clinical development programs.
3:10 The Parker Institute’s Collaborative and Integrated Approach to Immuno-Oncology Biomarkers
Theresa LaVallee, Ph.D., Head of Translational Medicine, The Parker Institute for Cancer Immunotherapy
The Parker Institute for Cancer Immunotherapy’s mission is to accelerate the development of breakthrough immune therapies to turn cancer into a curable disease. Through collaborative efforts utilizing innovative technologies and integrating clinical and correlative datasets, Parker is advancing the understanding and utilization of immuno-oncology biomarkers.
3:40 High Definition Multiplexing for Biomarker Discovery
Stephanie Walter, Ph.D., R&D Team leader, Ultivue
Biomarker discovery in immuno-oncology requires the analysis of multiple protein markers (n>4) with their spatial relationships at an amenable throughput. The scrutiny of the tumor micro-environment demands whole-slide multiplexed images featuring immune and tumor cells. Ultivue's InSituPlex platform fulfills this need with the data reproducibility relevant to CDx.
4:10 How to Accelerate the Development of Biomarkers through Consortia: Application to Immuno-Oncology
Vanessa Tumilasci, Ph.D., Project Director, Trans-Hit Bio
4:25 PANEL DISCUSSION: Integrated Approaches to IO Biomarkers and Companion Dx
Moderator: Robert D. Loberg, Ph.D., Executive Director of Clinical Biomarkers & Diagnostics, Amgen, Inc.
Panelists: Theresa LaVallee, Ph.D., Head of Translational Medicine, The Parker Institute for Cancer Immunotherapy
Seth Pollack, MD, Assistant Member, Fred Hutchinson Cancer Research Center, Clinical Research Division; Assistant Professor, University of Washington, Division of Oncology, Fred Hutchinson Cancer Research Center
Zhen Su, M.D., MBA, Vice President & Head of Global Medical Affairs, EMD Serono
4:40 Refreshment Break and Transition to Plenary Session
5:00 Plenary Keynote Session (click here for more details)
6:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing
7:30 Close of Day
Tuesday, February 13
7:30 am Registration Open and Morning Coffee
8:00 Plenary Keynote Session (click here for more details)
9:00 Refreshment Break in the Exhibit Hall with Poster Viewing
10:05 Chairperson’s Remarks
Stefanie Jeffrey, M.D., John and Marva Warnock Professor, Surgery; Chief, Surgical Oncology Research, Stanford University School of Medicine
10:15 FEATURED PRESENTATION: Circulating Tumor Cells: History and Future Perspectives
Jonathan W. Uhr, M.D., Professor Emeritus, Immunology, University of Texas Southwestern Medical Center
The modern era of CTC analysis began 2 decades ago and gained momentum when CellSearch was approved by the FDA. The changes of CTC counts allowed prognostication of patients with growing cancers. Genotypic and immunophenotypic analyses will play critical roles in personalized treatment for cancer.
10:45 Microfluidic Cell Tethering to Identify Anti-Metastasis Drugs
Stuart S. Martin, Ph.D., Professor, Physiology, Marlene and Stewart Greenebaum NCI Comprehensive Cancer Center, University of Maryland School of Medicine
11:15 Dissecting Mechanisms of Breast Cancer Metastasis Using Patient-Derived Circulating Tumor Cells
Min Yu, M.D., Ph.D., Assistant Professor, Stem Cell Biology and Regenerative Medicine Member, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California
Circulating tumor cells (CTCs) are expected to contain metastasis-initiating cells that can shed light on the mechanisms of cancer metastasis. However, due to limited patient-derived material, the metastatic capability of CTCs has yet to be proved. Using our recently established patient-derived CTC lines, we found that different patient CTC lines demonstrated distinct metastatic tissue tropisms in immunodeficient mice and identified associated pathways to specific organs via RNA-seq and ATAC-seq analysis.
11:45 Isolating and Characterizing Clinically Relevant CTCs Using the VTX-1 Liquid Biopsy System
Elodie Sollier, Ph.D., CSO, Research and Development, Vortex Biosciences, Inc.
12:15 pm Session Break
12:25 Luncheon Presentation: Achieving Clinical Utility of Cell-Based Liquid Biopsy
Mark Connelly, PhD, Chief Industrial Operation, R&D Officer, US Menarini Silicon Biosystems Inc
Clinical studies have demonstrated that CTCs enumeration is a strong, independent predictor of overall and progression-free survival in metastatic breast, prostate and colorectal cancer at any time during the course of disease. The field agrees that for a full adoption of liquid biopsy as clinical diagnostic tool to guide therapeutic decision the molecular characterization of CTCs is necessary.
12:55 Session Break
1:25 Refreshment Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Remarks
Steven A. Soper, Ph.D., Foundation Distinguished Professor, Chemistry, Mechanical Engineering, University of Kansas
2:10 CTC Isolation Platforms and Using CTCs for Monitoring Therapy Responses
Z. Hugh Fan, Ph.D., Professor, Mechanical and Aerospace Engineering, University of Florida
We will present our recent results on using microfluidic devices for enumerating circulating tumor cells (CTCs) in the blood samples of pancreatic cancer patients and using CTCs as a biomarker for monitoring the responses of cancer patients to anticancer therapy. Other platforms for CTC isolation and analysis will be reviewed and examined. Parameters for platform comparison will be discussed.
2:40 Diagnosis of Traumatic Brain Injury Using Machine Learning-Based miRNA Signatures in Nanomagnetically Isolated Brain-Derived Exosomes
Jin A. Ko, Ph.D. Candidate, Bioengineering and Electrical & Systems Engineering, University of Pennsylvania
Circulating exosomes contain molecular information, presenting an opportunity in diagnostics. While microfluidics can isolate cells from complex samples, scaling these approaches for exosomes is limited by low throughput and clogging of nanofluidics. Analysis of exosomes is confounded by heterogeneity between patients. We developed a device, wherein millions of nanofluidic channels operate in parallel, increasing throughput and eliminating clogging. We isolate exosomes from blood, profile their RNA cargo, and apply machine learning to generate a diagnosis.
3:10 Stabilization of Circulating Extracellular Vesicle Levels Using a Novel Blood Collection Tube
Nicholas George, Ph.D., Senior Research Scientist, Research and Development, Streck
Extracellular vesicles (EVs), including exosomes and microvesicles, harbor a multitude of cellular molecules and therefore reflect the activation status and identity of the parental cell. Liquid biopsy protocols are expeditiously incorporating EVs as disease status biomarkers. However, a significant obstacle in blood-based workflows is the instability of blood cells and increases in the concentration of non-disease EVs. Here we describe utility of a blood collection tube intended for stabilizing draw-time concentrations of patient EVs.
3:40 Genomic Instability of Circulating Prostate Cancer CTCs
Sabine Mai, Ph.D., Senior Investigator, Manitoba Institute of Cell Biology/RIOH, Professor, University of Manitoba, Director, The Genomic Centre for Cancer Research and Diagnosis
4:10 Valentine’s Day Celebration in the Exhibit Hall with Poster Viewing
5:00 Breakout Discussions in the Exhibit Hall
These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.
Challenges of Moving Liquid Biopsy Technologies/Assays Forward to Clinical Utility
Lynn R. Sorbara, Ph.D., Program Director, Cancer Biomarker Research Group, National Cancer Institute
Anthony Dickherber, Ph.D., Program Director, Center for Strategic Scientific Initiatives, National Cancer Institute
- How can we tie together the clinical significance to detection of circulating nucleic acid markers and CTCs?
- What are the major stumbling blocks?
- IP issues? MTAs? CDAs?
- Access to more or better tools?
- Sample or patient accrual? Storage of biospecimens?
- What are ways that we can enhance collaboration and exchange of information and data?
CTC Capture, Interrogation, and Culture
Richard J. Cote, M.D., FRCPath, FCAP, Professor, Joseph R. Coulter Jr. Chair, Pathology & Laboratory Medicine; Professor, Biochemistry and Molecular Biology; Chief of Pathology, Jackson Memorial Hospital
- Live CTC capture
- Conditions for expansion and propagation of CTC
- Biomimetic Systems for CTC propagation
- Novel interrogation of CTC
Tumor Tissue Extracellular Vesicles
Jan Lötvall, Ph.D., Professor, Krefting Research Centre, University of Gothenburg, Sweden, Chief Scientist, Codiak BioSciences, Cambridge, MA
- Extracellular vesicle diversity
- Isolation of extracellular vesicle subpopulations
- Clinical validation of extracellular vesicle biomarkers
- Multiplexing extracellular vesicle data
Liquid Biopsy for Brain Tumors
Brian V. Nahed, M.D., MSc, Associate Professor, Neurosurgery, Harvard Medical School; Associate Program Director, MGH
- Brain tumor diagnosis, monitoring, and treatment
- Blood tests / biomarkers
- Mutational analysis of brain tumors and blood
Gaps and Opportunities in Biomarker Development for IO Therapies
Zhen Su, M.D., MBA, Vice President & Head of Global Medical Affairs, EMD Serono
- Need for longitudinal monitoring of immune response
- Deeper understanding of PDx mechanisms of treatment resistance
- Identifying biomarkers for combination drug development
Tumor Mutation Burden as an IO Biomarker
Terri McClanahan, Ph.D., Executive Director, Profiling & Expression, Translational Medicine, Merck Research Laboratories
- Need for longitudinal monitoring of immune response
- Deeper understanding of PDx mechanisms of treatment resistance
- Identifying biomarkers for combination drug development
6:00 Close of Day
Wednesday, February 14
7:30 am Registration Open and Morning Coffee
8:00 Plenary Keynote Session (click here for more details)
10:00 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall
10:50 Chairperson’s Remarks
Scott D. Patterson, Ph.D., Vice President, Biomarker Sciences, Gilead Sciences, Inc
11:00 High-Content Molecular Profiling in Development of Combination Immunotherapies: Making Rational from Non-Rational
Ruslan Novosiadly, Ph.D., Senior Research Advisor, Cancer Immunobiology, Biomarkers, Eli Lilly
Biomarker discovery paradigm in immuno-oncology has been shifting from hypothesis-testing to hypothesis-generating mode. High-throughput, high-content molecular and immune profiling enables comprehensive biomarker evaluation. Interrogation of mechanistic biomarkers in preclinical mouse tumor models helps identify and guide rational combinations in immune-oncology.
11:30 Next Generation Biomarkers for the Era of Combination Cancer Immunotherapies
Sarah Javaid, Ph.D., Senior Scientist, Discovery Pharmacogenomics, Genetics, Pharmacogenomics, Merck
Immune checkpoint blockade therapies are revolutionizing the standard cancer treatment. Despite the current success of these therapies, not all patients respond to immunotherapy and even those that do often experience toxicities. Combination approaches are the keys to improving clinical response. Novel high throughput technologies enable us to understand the mechanisms underlying the complex interactions between the immune system and cancer and identify predictive biomarkers for patients.
12:00 pm PANEL DISCUSSION: Biomarkers for Combination Cancer Immunotherapy
Moderator: Scott D. Patterson, Ph.D., Vice President, Biomarker Sciences, Gilead Sciences, Inc.
Panelists: Paul Robbins, Senior Director, Early Development and Translational Oncology, Pfizer
Mark Gardner, CEO, OmniSeq Inc
- Current and emerging biomarkers for patient selection for immunooncology therapies – will current assays be completely superseded?
- Beyond the biopsy - what future blood-based biomarkers?
- NGS panels have arrived – are we ready for complex transcript panels?
- Harmonization of multiple assays for the same biomarker(s) – can this be achieved during development?
12:30 Session Break
12:40 Enjoy Lunch on Your Own
1:10 Dessert Break in the Exhibit Hall and Last Chance for Poster Viewing
1:50 Chairperson’s Remarks
Shannon L. Stott, Ph.D., Assistant Professor, Department of Medicine, Massachusetts General Hospital, Harvard Medical School; BioMEMS Resource Center, The MGH Cancer Center
2:00 Liquid Biopsy for Brain Tumors
Brian V. Nahed, M.D., MSc, Associate Professor, Neurosurgery, Harvard Medical School; Associate Program Director; MGH Neurosurgery Residency, Massachusetts General Hospital
Despite advances in imaging, patients undergo surgery to establish a diagnosis followed by chemoradiation. Methods to monitor and detect response, recurrence, and distinguish it from post-treatment effects using magnetic resonance imaging are severely limited, and ultimately patients undergo additional surgery for diagnosis. Our laboratory has developed a microfluidic device to capture and analyze circulating tumor cells and extra-cellular vesicles which provides real-time mutational information about a patient’s brain tumor.
2:20 Extracellular Vesicles and Platelets: A Strong Friendship in CancerLand
Bakhos A. Tannous, Ph.D., Associate Professor of Neurology, Harvard Medical School; Director, Experimental Therapeutics and Molecular Imaging Lab; Director, Interdepartmental Neuroscience Center; Director, MGH Viral Vector Development Facility, Massachusetts General Hospital
Tumor-educated blood platelets (TEPs) are implicated as central players in the systemic and local responses to tumor growth, thereby altering their RNA profile. In this presentation, we will discuss the potential use of TEPs for pan-cancer, multiclass cancer, and companion diagnostics, enabling clinical advances in blood-based “liquid biopsies.” We will also discuss TEP-extracellular vesicles interactions and potential exchange of biomarker materials.
2:40 Tumor Tissue Extracellular Vesicles for Biomarker Discovery – RNA, DNA and Protein
Jan O. Lötvall, Ph.D., Professor, Krefting Research Centre, University of Gothenburg, Sweden; Chief Scientist, Codiak BioSciences
This presentation will discuss the diversity of extracellular vesicles, specifically in human tumor microenvironments. I will also introduce the concept of identifying and validating multiplex biomarker candidates, based on data acquired specifically from tumor tissue extracellular vesicles. The biomarker candidates are developed based on information on vesicle-associated cancer proteins, DNA and RNA.
3:00 PANEL DISCUSSION
3:30 Session Break
3:40 Chairperson’s Remarks
Joseph A. Fraietta, Ph.D., Associate Director, Product Development, Center for Advanced Cellular Therapeutics, University of Pennsylvania
3:45 Changes in Circulating Leukocyte Quantities Inform Dosing Decisions and Pharmacodynamic Effects in Combination Trials of Immune Oncology Therapeutics
Nathan Standifer, Ph.D., Senior Scientist, Clinical Pharmacology and DMPK, MedImmune
Immune oncology (IO) therapeutics are designed to activate exhausted T cells, thereby enhancing tumor-specific immune responses. While IO compounds have demonstrated substantial efficacy, most treated patients fail to respond. As such, trials of IO therapeutics combined with small molecule inhibitors have been undertaken. This presentation will describe the use of flow cytometry-based assays to monitor circulating leukocyte populations to characterize pharmacodynamic effects and inform dosing decisions in such combination trials.
4:15 What Does It Take to Make Flow Cytometry a Routine Assay in the Clinic and as PDx?
Iulian Pruteanu-Malinici, Ph.D., Biostatistics, Investigator II/Lab Head at Novartis Institutes for BioMedical Research (NIBR)
Here, we present a flow cytometry based framework that, when combined with state of the art bioinformatics, enables for the discovery of biomarkers that predict clinical response of CTL019 therapeutic products. The aim is to identify a biomarker signature that correlates with clinical response; to measure the predictive power of each signature, a T-test is used to evaluate the difference between measured phenotypes’ cell frequencies (the number of cells in that phenotype divided by the total number of cells in the parent population) among Complete Responders (CR) and Non-Responders (NR). The most statistically significant phenotypes are then selected for manual confirmation using FlowJo.
4:45 Biomarkers for CAR T Cell Therapy and Combinations
Joseph A. Fraietta, Ph.D., Associate Director, Product Development, Center for Advanced Cellular Therapeutics, University of Pennsylvania
Chimeric antigen receptor (CAR) T cells that target tumor antigens can induce remissions in patients with hematologic malignancies, but only in a subset of subjects with CLL. The mechanisms that potentiate CAR T cell potency are largely unknown. Here we describe a remarkable case that helps clarify determinants of persistence and points to a modifiable epigenetic pathway which may increase anti-tumor activity and therapeutic efficacy of gene-modified T cells.
5:15 Close of Conference Program