Cambridge Healthtech Institute’s 2nd Annual
Biomarkers for Immunotherapy
Predictive and Prognostic Biomarker Discovery for Successful Therapy
7-8 May 2019
Despite the revolution of immunotherapy for cancer treatment in recent years, many treated patients do not respond, not mentioning some potential serious side effects associated with these treatments. There is a pressing need for the discovery of prognostic
and predictive biomarkers that will improve the selection of patients who will best respond to therapy and help tailor therapy regimens. CHI’s Second Annual “Biomarkers for Immunotherapy” will bring together biomarkers experts from
industry and academia to address advances in the discovery and development of predictive and prognostic biomarkers for immunotherapy.
Final Agenda
Day 1 | Day 2 | Download Brochure | Register
SC2: Biomarkers in Liquid Biopsy: CTCs, ctDNA and Exosomes
Lorena Diéguez, PhD, Group Leader, Department of Life Sciences, Nano4Health Unit, Medical Devices Research Group, International Iberian Nanotechnology Laboratory, Portugal
Roberto Piñeiro Cid, PhD, Cancer Modeling Lab, Instituto de Investigación Sanitaria de Santiago de Compostela- Roche-Chus Joint Unit, Spain
Biomarkers for early disease detection, therapeutic efficacy monitoring and outcome prediction are the key to precision medicine. Liquid Biopsy studies disease biomarkers in body fluids and can be paramount for precision medicine in cancer. The analysis
of biomarkers in peripheral blood improves cancer diagnosis and treatment success. This course will give you a comprehensive overview and update on the established biomarkers, available technologies and clinical applications of liquid biopsy.
*Separate registration required.
TUESDAY 7 MAY
08:00 Registration and Morning Coffee
08:55 Organizer’s Opening Remarks
Ngoc 'Emily' Le, PhD, Conference Producer, Cambridge Healthtech Institute, United States
09:00 Chairperson's Remarks
Ed Schuuring, PhD, Professor & Head, Molecular Pathology, University Medical Center Groningen, The Netherlands
09:05 Immune Contexture Heterogeneity and Clinical Impact
Jérôme
Galon, Director, Integrative Cancer Immunology Laboratory, Cordeliers Research Center, Research INSERM (French NIH) (first class, DR1), France
We developed and validated worldwide a standardized digital-pathology-based immune assay, “Immunoscore”, with prognostic power superior to the currently used cancer staging-system. Immunoscore and immunoediting were demonstrated to affect
metastatic dissemination in humans. The newly-proposed “parallel immune selection model” of tumor evolution incorporates the effects of the immune system in shaping metastatic spread. The impact of the immune contexture on predicting
response to immunotherapy, including CAR-T cells, will also be discussed.
09:35 The 10,000 Immunomes Project: Building a Resource for Human Immunology
Sanchita Bhattacharya, PhD, Bioinformatics Project Scientist, Bakar Computational Health Sciences Institute, University of California San Francisco, United States
One of the major barriers for understanding human immunological mechanisms is that immune assays have not been reproducibly characterized for a sufficiently large and diverse healthy human cohort. Here, we present the 10,000 Immunomes Project (10KIP),
a framework for growing a diverse human immunology reference, from ImmPort, a publicly available resource of subject-level immunology data.
10:05 Comparing Immune Cell Populations and Novel Biomarkers in Subtypes of NSCLC
Anna Juncker-Jensen, PhD, Medical Science Liasion, NeoGenomics Laboratories, USA
10:35 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing
11:15 Chairperson's Remarks
Ed Schuuring, PhD, Professor & Head, Molecular Pathology, University Medical Center Groningen, The Netherlands
11:15 KEYNOTE PRESENTATION: Development of a TMB Assay and the Challenges of Harmonizing across Products
Michael Doherty, Senior Vice President, Head of Product Development, Foundation Medicine, United States
A novel, technically robust, blood-based assay to measure TMB in plasma (bTMB) that is distinct from tissue-based approaches will be described. Using a retrospective analysis of two large randomized trials as test and validation studies, we show that
bTMB reproducibly identifies patients who derive clinically significant improvements in progression-free survival from atezolizumab (an anti-PD-L1) in second-line and higher NSCLC. Our data show that high bTMB is a clinically actionable biomarker
for atezolizumab in NSCLC. Challenges and efforts to harmonize across products will also be discussed.
11:45 NEW: Is It Time for an International Genomic Reference Panel for MSI and TMB?
Leandro Lo-Cascio, PhD, Standard Development Senior Scientist, Advanced Therapies, National Institute for Biological Standards and Control (NIBSC)
For the generation of a reference material our approach includes sourcing and characterization of MSS and MSI-H cell lines, as well as generation and characterization of novel MSI-H cell lines via CRISPR-engineering. At present a panel of 10 cancer
and control cell lines has been sourced and characterised for MSI using a PCR-based approach. WGS and targeted panel sequencing was performed on candidate cell lines. MSIsensor was used to calculate MSI status, to confirm PCR-based findings. Further
characterization will be performed with other commercially available MSI assays and further bioinformatics approaches. Furthermore, we are aiming to generate MSI-H cell lines via CRISPR, targeting genes of the MMR system in a MSS cell line. Benefits
of this approach will be the generation of MSI-H/MSS paired samples. MSI and TMB represent useful biomarkers to select cancer patients that will benefit from targeted therapies. Standards are required for accurate and sensitive diagnostic testing.
Thus, we appreciate the necessity of a reference material intended as a non-assay-specific primary standard to calibrate MSI and TMB measurements.
12:15 Expression of Endogenous Retrovirus as a Potential Biomarker of Response to Immune Checkpoint Therapy in Low Mutation Burden Cancers
Shridar
Ganesan, MD, PhD, Chief, Molecular Oncology; Associate Director, Translational Research; Omar Boraie Chair, Genomic Science, Rutgers University, United States
To better understand response of low mutation burden cancers to ICB, we investigated the expression of endogenous retroviruses (ERVs) and their association with markers of immune infiltration and immune checkpoint activation. Endogenous retroviruses
are normally not expressed in most somatic tissues, but abnormal expression has been reported in multiple cancer types. Expression of certain classes of ERV was associated with markers of immune activation in several tumor classes, but most strikingly
in clear cell renal cancer. ERV expression was associated with evidence of chromatin abnormalities, and with increased response to immune checkpoint blockade in ccRCC. These observations suggest that ERV expression may be novel biomarker of response
to ICB in certain cancers including ccRCC.
12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
14:15 Chairperson's Remarks
Shridar Ganesan, MD, PhD, Chief, Molecular Oncology; Associate Director, Translational Research; Omar Boraie Chair, Genomic Science, Rutgers University, United States
14:20 Circulating Tumor DNA as a Molecular Bloodborne-Based Biomarker to Predict Tumor Response in Lung Cancer Patients Treated with Immunotherapy
Ed Schuuring, PhD,
Professor & Head, Molecular Pathology, University Medical Center Groningen, The Netherlands
A significant minority of patients treated with immune checkpoint inhibitors shows durable responses but no adequate biomarkers are available for predicting which patients will benefit. Immunotherapy is expensive and potentially toxic. Tumor response
is monitored by tumor volume using CT scanning. The aim of our study is to assess plasma levels of non-targetable tumor-specific mutations as molecular biomarkers and monitoring tool for durable responses to immunotherapy in advanced NSCLC.
14:50 Tumor Immunoprofiling: Novel Tissue-Based Biomarkers in Cancer Immunotherapy
Nicolas A. Giraldo-Castillo, MD, PhD, Pathology Resident, Johns Hopkins University School of Medicine, United States
Therapeutic blockade of the PD-1/PD-L1 checkpoint has been embraced as a strategy to enhance antitumor T-cell immunity, with durable efficacy in multiple tumor types. The best-studied biomarker to predict response to these agents is PD-L1 protein
expression, measured by immunohistochemistry and graded “positive” or “negative.” Using digital pathology-assisted methods, our laboratory has found that quantitative assessments of PD-1+ and PD-L1+ cell densities,
as well as geographic interactions between these two cell populations, correlate with clinical response to anti-PD-1 therapy in Merkel cell carcinoma, melanoma, and renal cell carcinoma and is superior to binomial scoring systems.
15:20 Implementing Immunosequencing as New Molecular Biomarkers of Response to Immunotherapy
Catherine Sanders, PhD, Senior Director, Research and Business Development, Adaptive Biotechnologies, USA
Adaptive Biotechnologies’ immunosequencing technology combines bias-controlled multiplex PCR, high-throughput sequencing, and sophisticated bioinformatics. In solid tumors, the immunoSEQ Assay accurately quantifies TIL density and clonality,
with preclinical and clinical applications to inform repertoire changes in response to single agent or combination therapies that have potential prognostic and predictive value.
15:50 Immunophenotyping and Functional Assays for Predictive Marker Discovery
Junxia Wang, PhD,
Director, Analytical Development, Mustang Bio, Inc., United States
The discovery and development of predictive for CAR T cells have unique challenges as compared to conventional drugs as the clinical outcome is largely dependent on a viable cellular drug. To overcome the challenges, we have implemented an integrated
clinical and CMC biomarker strategy to extend our biomarker study for CAR T cells to include the characterization of the cells prior to engineering and the final product at the site of manufacturing facility. To this purpose, a series of immunophenotyping
and functional assays have been developed for the discovery of predictive markers of treatment efficacy and toxicity.
16:20 Refreshment Break in the Exhibit Hall with Poster Viewing
17:00 Breakout Discussions View Details
18:00 Welcome Reception in the Exhibit Hall with Poster Viewing
19:00 Close of Day
Day 1 | Day 2 | Download Brochure
WEDNESDAY 8 MAY
08:00 Registration and Morning Coffee
09:00 Chairperson's Remarks
Christopher M. Hartshorn, PhD, Program Director, NIH NCI, United States
09:05 Current Initiatives and Research Efforts at the National Cancer Institute Dedicated to Cancer Immunotherapy
Christopher M. Hartshorn, PhD, Program Director, NIH NCI, United States
The US National Cancer Institute (NCI) of the National Institutes of Health has played an integral role in the research and funding of cancer immunotherapies over the last several decades. As the core understanding as to the interface between
cancer biology and immunological response have evolved, so has the NCI’s conceptual vision of this unique therapeutic modality and the needs of the field. This talk will focus on the most recent and relevant efforts focused at developing
markers and tools for patient stratification, deciphering the complex nature of responders vs non-responders, and earlier intervention after dosing.
09:35 Interpretation and Validation of Longitudinal Serum Tumor Biomarker Changes for Early Prediction of Immunotherapy Non-Responsiveness
Huub H. van Rossum, PhD, EuSpLM, Specialist, Laboratory Medicine and Clinical Chemistry, Laboratory Medicine, The Netherlands Cancer Institute, The Netherlands
For NSCLC, only a modest number of patients treated with immune checkpoint inhibitors will respond to this treatment. Serum tumor biomarkers may be of value and alert the clinician of possible treatment failure. The Re-marker platform was
developed to support basal longitudinal biomarker investigations including BReC-plot generation and the diagnostic validation of biomarker-response based tests. Using this tool, biomarker response-based tests could be designed that accurately
predict non-responsiveness to immunotherapy.
10:05 Predicting Immunotherapy Response and Toxicity in Melanoma
Helen Rizos,
PhD, Head, Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Australia
There is an urgent need to identify biomarkers that accurately predict for treatment response, and guide the selection of novel combination therapies for patients who acquire resistance. There is also a requirement to accurately predict whether
response will be associated with significant adverse events. In this presentation, the utility of circulating biomarkers as predictive and prognostic markers in melanoma, including circulating cytokines, exosomes and circulating tumour
DNA, will be discussed.
10:35 Highly-Characterized TMB Reference Standards to Standardize and Harmonize TMB Measurements
Dan Brudzewsky, Field Application Scientist, Clinical Genomics, SeraCare Life Sciences, USA
Tumor mutational burden (TMB) is a pan-cancer biomarker for assessing immuno-oncology drug response. SeraCare is collaborating with FOCR and IQN-Path to develop TMB reference standards with confirmed mutational burden to standardize and harmonize
TMB measurements. We describe the characterization of a panel of gDNA and FFPE-based TMB reference materials by WES.
11:05 Coffee Break in the Exhibit Hall with Poster Viewing
11:35 Moderator’s Remarks
Charlotte Ryckman, Associate, Covington & Burling LLP, Belgium
11:45 Precision Diagnostics in Oncology: Expanding Roles of Liquid Biopsies
Nitzan Rosenfeld, PhD, Senior Group Leader, Cancer Research UK Cambridge Institute, University of Cambridge; CSO, Inivata Ltd., United Kingdom
Effective clinical management relies on accurate diagnostic information, which requires effective techniques and the right samples. Next generation sequencing can provide a wealth of information, but implementing innovative technologies into
clinical routine can be a challenge. We’ll examine how analysis of cell-free DNA can provide an opportunity to re-examine many of the current clinical decision points, and a test case for adoption of new diagnostic tools.
12:15 Legal and Regulatory Developments in Precision Medicine and Diagnostic Devices
Erik Vollebregt, Partner, Axon Lawyers, The Netherlands
- What changes will be brought about by the IVDR?
- What is the impact of the GDPR in the field of precision medicine and diagnostic devices?
- What are the practical implications of implementation of new European regulations?
- What are the consequences of the interplay of the IVDR and the GDPR?
12:45 PANEL DISCUSSION: Challenges and Opportunities in European Diagnostic Investments
Moderator:
Philippe Peltier, Partner, Kurma Partners, France
Panelists:
Florian Kainzinger, PhD, Managing Partner, Founder, Think.Health Ventures, Germany
Seppo
Mäkinen, Partner, Pathena Investments
- What is different in Europe versus other markets (e.g., US and Israel). How do different European markets compare?
- What has changed in the landscape of European investments over the past few years? What can be improved?
- The role of regulators and governments
- How can start-ups stand out and get attention in the current landscape?
13:30 Close of Biomarkers for Immunotherapy
Day 1 | Day 2 | Download Brochure