Cambridge Healthtech Institute’s Second Annual
Biomarkers for Cancer Immunotherapy and Combinations
Immunopheno- and Genotyping to Define Tumor-Immune Interactions
August 20-21, 2018 | Grand Hyatt Washington | Washington, DC
The heterogeneity of cancer, and the complex interaction of cancer and immune cells, require sophisticated phenotypic and genotypic testing in order to answer important questions for new immuno-oncology agent discovery and clinical development. Cell-based biomarkers, biomarkers of tumor microenvironment, neoantigens, and tumor mutation burden are some of the classes of biomarkers that guide clinical development and patient care in immune-oncology. Cambridge Healthtech Institute’s Second Annual Biomarkers for Cancer Immunotherapy and Combinations is designed to feature cutting edge diagnostics technologies and their applications for new IO biomarkers identification and validation.
Final Agenda
MONDAY, AUGUST 20
12:00 pm Main Conference Registration (Independence Foyer)
1:30 Chairperson’s Opening Remarks
Neeraj Adya, PhD, Director, Pharmacodiagnostics Translational Medicine, Bristol-Myers Squibb
1:40 Using Single-cell RNAseq to Characterize the Molecular Effects of IO Therapy.
Katie Streicher, PhD, Associate Director, Translational Medicine, Medimmune
Numerous IO combinations are currently in clinical trials across multiple tumor types; however, how each combination modifies the tumor microenvironment is not well understood. Using single cell RNA sequencing and ex vivo tumor models, it is possible to systematically characterize the downstream cellular and molecular effects of different treatment modalities, potentially leading to the identification of novel biomarkers that could increase treatment response.
2:10 Advancing Precision Oncology: Emerging Biomarkers and Pharmacodiagnostic Tools
Neeraj Adya, PhD, Director, Pharmacodiagnostics Translational Medicine, Bristol-Myers Squibb
The use of biomarkers in cancer treatment has allowed for increased patient segmentation. This has been enabled by advances in development of new biomarkers that allow for more comprehensive characterization of the tumor microenvironment. This talk will focus on ongoing use of emerging biomarkers like TMB, gene expression profiling and use of composite biomarkers as pharmacodiagnostic tools that are paving the path towards precision medicine.
2:40 The Timing, Placement and Impact Of Biomarkers
Meghna Das Thakur, PhD, Scientist, Oncology Biomarker Development, Genentech
Biomarkers are vital in both early and late stage clinical trials even though their context and use can be dramatically different. Whether used to inform safety, PK/PD, dose and schedule or for patient selection and sub group analyses, biomarkers are becoming an integral part of clinical development.
3:10 Transforming Immuno-Oncology with ctRNA + ctDNA Liquid Biopsy Solutions
Shidong Jia, MD, PhD, CEO, Predicine
Determining which patients would derive clinical benefit from immunotherapy is a compelling clinical question. Biomarkers have been shown to predict therapy outcome in various types of cancer patients. This talk will focus on the development and clinical applications of circulating RNA and DNA-based liquid biopsy tests in biomarker-driven clinical trials.
3:25 Sponsored Presentation (Opportunity Available)
3:40 Networking Coffee Break (Independence Foyer)
4:15 pm Chairperson’s Remarks
Charles Mathews, Principal, ClearView Healthcare Partners
4:25 - 5:45 pm Global Dx Insights: Policy and Prediction for Diagnostics
Moderator: Cecilia Schott, PhD, Former Vice President, Precision Medicine, AstraZeneca
- Will value-based medicine replace fee-for-service?
- PAMA impact on reimbursement
- Changes in LDT oversight policy
- Changing landscape of IVD regulation in U.K. and Europe after Brexit
- What is the future of molecular diagnostics in medical care?
- How will these policy changes affect the patient?
Panelists:
Dennis J. Dietzen, PhD, DABCC, FAACC, President, AACC; Professor of Pathology & Immunology and Pediatrics, Washington University School of Medicine; Medical Director of Laboratory Services, St. Louis Children’s Hospital
John Leite, PhD, Vice President, Strategic Partnerships, Corporate and Business Development, Illumina
J. Leonard Lichtenfeld, MD, MACP, Deputy CMO, American Cancer Society, Inc.
Victoria M. Pratt, PhD, FACMG, Director, Pharmacogenomics and Molecular Genetics Laboratories, Department of Medical and Molecular Genetics, Indiana University School of Medicine (AMP President-Elect)
Susan Van Meter, Executive Director, AdvaMedDx
Ian S. Young, MD, PhD, Chief Scientific Advisor, Department of Health (Northern Ireland) and President, Association for Clinical Biochemistry and Laboratory Medicine (ACB), UK
5:45 Wine & Cheese Pairing Welcome Reception in the Exhibit Hall with Poster Viewing (Independence Ballroom)
7:00 Close of Day
TUESDAY, AUGUST 21
7:15 am Registration (Independence Foyer)
7:30 Problem Solving Breakout Sessions with Continental Breakfast (Independence F-I)
This session features various discussion groups that are led by a moderator/s who ensures focused conversations around the key issues listed. Attendees choose to join a specific group and the small, informal setting facilitates sharing of ideas and active networking. Continental breakfast is available for all participants.
Cell-Based Biomarkers
Moderator: Katie Streicher, PhD, Associate Director, Translational Medicine, Medimmune
- Integrating cell-based biomarkers with TMB and other genomic analyses
- Value of cell-based biomarkers in characterizing mechanisms of resistance
- Challenges in identifying markers that represent diversity of the tumor micro-environment
Challenges To Companion Diagnostic Development In Multiplex Biomarkers
Moderator: Deepti Aurora-Garg, PhD, Director, Companion Diagnostics, Translational Medicine, Merck & Co.
- Regulatory hurdles
- High cost of test. Reimbursement issues
- Challenges of incorporating into prospective clinical trials
8:30 Chairperson’s Remarks
Deepti Aurora-Garg, PhD, Director, Companion Diagnostics, Translational Medicine, Merck & Co.
8:35 Role of Gene Alternations (Tumor Mutation Burden) and Gene Expression Signatures in Recurrent and Metastatic Head and Neck Cancer Treated with Keytruda
Deepti Aurora-Garg, PhD, Director, Companion Diagnostics, Translational Medicine, Merck & Co.
Checkpoint inhibitors boost the immune system and target tumor cells through various mechanisms. There is a strong crosstalk between tumor cells and the tumor microenvironment that cannot be understood on the basis of a single biomarker. Hence multiplex biomarkers like gene expression signatures and tumor mutation burden are gaining importance to identify patients most likely to respond. A case study of these cutting edge biomarkers is presented in recurrent/metastatic head and neck cancer.
NEW:9:05 Progress Toward a Liquid Biopsy for Immune Monitoring
Sam M. Hanash, MD, PhD, Professor, Molecular Pathology, Division of Pathology Lab Medicine, The University of Texas MD Anderson Cancer Center
This presentation will review progress toward elucidating the diverse mechanisms through which tumor cells evade immune monitoring.
10:05 Coffee Break in the Exhibit Hall with Poster Viewing (Independence Ballroom)
11:00 Optimization and Validation of Multiplex Immunofluorescence and Multispectral Imaging for Immuno-Oncology
Jaime Rodriguez-Canales, MD, FEBP, Senior Pathologist, Translational Pathology Laboratory, MedImmune
Multiplex immunofluorescence (MIF) and multispectral imaging (MSI) using Vectra/Polaris™ (PerkinElmer) has become an important method to interrogate the immunological tumor microenvironment in tissue specimens. MIF/MSI can quantify individual markers, co-localize them to identify immune cell populations, and provide spatial distribution data of immune cells within the tissue. However, MIF/MSI can be challenging and requires careful optimization and validation. Here we will discuss the optimization strategy of MIF/MSI for immuno-oncology studies.
11:30 Pathologic Features of Response to Neoadjuvant Anti-Pd-1: A Proposal for Quantitative Immune-Related Pathologic Response Criteria (Irprc)
Janis M. Taube, MD, Director, Dermatopathology Division and Fellowship, Associate Professor of Dermatology, Pathology, and Oncology, Johns Hopkins University
A standardized approach to the assessment of pathologic response is necessary for reliable interpretation of the post-treatment resection specimens in patients receiving neoadjuvant anti-PD-1 therapy. Neoadjuvant specimens also provide a unique window into the mechanism of action of immune checkpoint blockade. The features of immune-mediated tumor clearance will be described, and a provisional, reproducible scoring system for pathologic response to neoadjuvant anti-PD-1 based on these features will be presented.
12:00 pm Multidimensional Biomarkers Using Gene Expression and Machine Learning
Natalie LaFranzo, PhD, Director, Scientific Projects and Market Development, Cofactor Genomics, Inc.
The success of immunotherapy development relies on robust approaches for characterizing and interpreting a patient’s immune system; specifically, the microenvironment surrounding a tumor. Using machine-learning informatics to interrogate gene expression profiles, Cofactor overcomes current challenges associated with commonly used methods, requiring very little tissue and reporting multidimensional markers.
12:30 Luncheon Presentation: Creating Predictive Diagnostics Measuring Tumor Infiltrating Immune Cells (TIICs)
Joseph Krueger, PhD, CSO, Flagship Biosciences
Many studies have indicated that the presence of Tumor Infiltrating Immune Cells (TIICs) are predictive of a higher response rate for immuno-oncology therapies. However, the inability to accurately and reproducibly measure TIICs in cancer biopsies in the clinical environment has limited the adoption of this approach by drug developers. In this presentation, we introduce methods for quantification of TIICs in cancer biopsies which are suitable for the clinical environment and regulatory approval.
1:00 Refreshment and Cookie Break in the Exhibit Hall with Poster Viewing (Independence Ballroom)
1:30 Chairperson’s Remarks
J. Joseph Melenhorst, PhD, Director, Product Development & Correlative Sciences Laboratories (PDCS); Adjunct Associate Professor, Center for Cellular Immunotherapies, University of Pennsylvania
1:35 Mechanisms of Resistance to Chimeric Antigen Receptor Therapy
J. Joseph Melenhorst, PhD, Director, Product Development & Correlative Sciences Laboratories (PDCS); Adjunct Associate Professor, Center for Cellular Immunotherapies, University of Pennsylvania
Synthetic biology has empowered patient T cells to eradicate cancer cells in patients who failed prior therapies. Some patients do, however, develop various forms of resistance to this very potent form of cancer therapy. In my talk I will discuss some such mechanisms, including the iatrogenic induction of CAR T cell resistance in a patient on one of our trials.
1:55 Beyond Uni-Variate Analyses Using Cytometry Data - Translation into Clinical Space
Iulian Pruteanu-Malinici, PhD, Biostatistics, Investigator II/Lab Head, 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.
2:15 The T Cell Repertoire Is Associated with Survival in Non-Small Cell Lung Cancer
Alex Reuben, PhD, Assistant Professor, Thoracic Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center
Tumor clearance is reliant on T cell responses. Therefore, we studied the T cell repertoire in patients with non-small cell lung cancer (NSCLC). Increased T cell heterogeneity was associated with shortened disease-free survival. Furthermore, a substantial proportion of T cells were shared between the normal lung and tumor and reactive to factors unrelated to the tumor. Our work sheds light on the challenges in harnessing T cell responses in NSCLC.
2:35 Enhancing CAR T Immunotherapy Safety and Efficacy: Is There a Role for CAR T Memory Stem Cells?
Devon J. Shedlock, Vice President, Preclinical Development, Poseida Therapeutics
To date, chimeric antigen receptor (CAR)-T immunotherapies have demonstrated unprecedented levels of efficacy against several hematologic tumor malignancies. However, safety and long-term durability continue to be major obstacles.
3:05 M2 Tumor-Associated Macrophages Co-Localize with T Regulatory Cells in the Pancreatic Tumor Microenvironment
Anna Juncker-Jensen, Senior Scientist, Pharma Services, NeoGenomics Laboratories
The immunosuppressive functions of M2 type tumor-associated macrophages (TAMs) (CD68+CD163+) can be exerted through release of cytokines and growth factors as well as via direct recruitment of T regulatory cells (Tregs)(CD3+CD4+FoxP3+). We have used MultiOmyx, a proprietary, immunofluorescence multiplexing assay to examine the spatial relationship between M1/M2 TAMs and Tregs in PDAC FFPE samples.
3:20 NEW: High Definition Multiplexing for Biomarker Strategies
Sean Downing, PhD, Director, Customer Engagement, Ultivue
Multiplexing in tissue sample is required to identify cell types, understand biological pathways, and map cellular interactions. Addressing this need, Ultivue’s InSituPlex technology provides high-throughput, whole-slide, multiplex tissue biomarker assays to help researchers tap into convoluted biomarker signatures and answer complex biological questions.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing (Independence Ballroom)
4:20 Chairperson’s Remarks
Iulian Pruteanu-Malinici, PhD, Biostatistics, Investigator II/Lab Head, Novartis Institutes for BioMedical Research (NIBR)
4:25 KEYNOTE PRESENTATION: Longitudinal Immune Profiling of Tumor Tissues
Ignacio I. Wistuba, MD, Professor & Chair, Department of Translational Molecular Pathology, Anderson Clinical Faculty Chair for Cancer Treatment and Research, UT MD Anderson Cancer Center
As new effective cancer immunotherapy strategies are being developed, there is an urgent need to develop and apply new immune-oncology molecular pathology tools to further investigate the role of immune response in cancer development and progression, and importantly to develop predictive biomarkers for these novel immunotherapies. Immune molecular pathology tools will be helpful to uncover the mechanism involved sensitivity and resistance, and potentially unveil mechanisms of immune toxicity.
4:55 Regulatory Perspective on Biomarkers for Cancer Immunotherapy
Aaron J. Schetter, PhD, Scientific Reviewer, Division of Molecular Genetics and Pathology, CDRH, FDA
There are a number of biomarkers used today – MSI, PD-L1 IHC, mutational burden – for considering patients for immunotherapy. This talk will share FDA perspective on existing and emerging biomarkers for cancer immunotherapy.
5:25 PANEL DISCUSSION: Translational Biomarkers in Immuno-Oncology
Moderator: Neeraj Adya, PhD, Director, Pharmacodiagnostics Translational Medicine, Bristol-Myers Squibb
Panelists:Iulian Pruteanu-Malinici, PhD, Biostatistics, Investigator II/Lab Head, Novartis Institutes for BioMedical Research (NIBR)
Katie Streicher, PhD, Associate Director, Translational Medicine, Medimmune
Aaron J. Schetter, PhD, Scientific Reviewer, Division of Molecular Genetics and Pathology, CDRH, FDA
- Unveiling Mechanism of Action and Resistance
- Identifying Indications
- Guiding Patient Selection
6:25 End of Biomarkers for Cancer Immunotherapy and Combination
6:00 Dinner Short Course Registration (Independence Foyer)