Cambridge Healthtech Institute’s 2nd Annual
Biomarkers for Immuno-Oncology
Enabling the Precise Selection of Immunotherapy for a Better Therapeutic Response
11-12 March 2020
Patient stratification and selection is a crucial step for those developing and providing immunotherapy. However, the heterogeneity of tumours makes it difficult to develop accurate predictive biomarkers for cancer patient populations. Thankfully there
is a significant effort across academia and industry to do just this. Combining outputs from genomics, transcriptomics, proteomics and metabolomics, as well as looking into more discreet blood niches, such as circulating tumour cells and exosomes,
may indeed provide the answers we need. At Cambridge Healthtech Institute’s 2nd Annual Biomarkers for Immuno-Oncology conference we will address this and more.
Final Agenda
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WEDNESDAY 11 MARCH
11:15 Organizer’s Remarks
Ngoc ‘Emily’ Le, PhD, Conference Producer, Cambridge Healthtech Institute
11:20 Chairperson’s Remarks
Andrew Sewell, PhD, Distinguished Research Professor and Wellcome Trust Senior Investigator, Infection & Immunity, Cardiff University School of Medicine
11:30 Strategies to Improve Antitumor Efficacy of Genetically Engineered T Cells
Stanley Riddell, MD, Scientific Director, Clinical Research, Fred Hutchinson Cancer Research Center; Professor, University of Washington School
of Medicine
Immune cells can be readily genetically modified to express natural tumor targeting antigen receptors or synthetic chimeric antigen receptors (CARs) that activate immune cell signaling pathways to result in destruction of tumor cells expressing the relevant
target molecule. The presentation will discuss advances in our understanding of receptor signaling and the development of strategies that combine therapeutic agents to improve efficacy and safely extend the spectrum of cancers that can be treated
with cell therapies.
12:00 PD-1 Antibodies Are Transforming Cancer Treatment
Roy D. Baynes, MD, PhD, Senior Vice President and Head, Global Clinical Development, CMO, Merck Sharpe & Dohme
PD-1 antibodies have shown significant activity as monotherapy across multiple cancer types and lines of therapy. Precision medicine tools have been used to identify subjects most likely to respond to PD-1 antibody monotherapy, to provide insight to potential
resistance mechanisms, and to inform combination therapies. A number of these combinations have demonstrated significant activity in additional tumor types and lines of therapy.
12:30 Enjoy Lunch on Your Own
13:30 Chairperson’s Opening Remarks
Sheeba Irshad, MD, PhD, Senior Clinical Lecturer, Cancer and Pharmaceutical Sciences, King’s College London
13:35 Mapping the Immune Landscape of High-Risk Chemotherapy Resistant Breast Cancers
Sheeba Irshad, MD, PhD, Senior Clinical Lecturer, Cancer and Pharmaceutical Sciences, King’s College London
Many patients with early breast cancers are treated with neoadjuvant chemotherapy (NACT). While those patients who achieve a pathological complete response (pCR) or minimal residual cancer burden (RCB)-I at surgery have an excellent long-term outcome,
the majority of patients with who have moderate (RCB-II) or extensive (RCB-III) residual disease suffer a much poorer outcome. An improved understanding of the biology and significance of the immune microenvironment (both within tumours and peripherally)
in chemotherapy-resistant breast cancers will inform the rational development of more effective therapy.
14:05 PD-L1 as a Companion Diagnostic for Tumors beyond Non-Small Cell Lung Cancer: It’s the Same Thing, Only Different
Kenneth Emancipator, MD, Executive Medical Director, Companion Diagnostics and Translational Medicine, Merck Sharp and Dohme (MSD)
The PD-L1 companion diagnostic had a huge impact on the clinical development of pembrolizumab, making it the first immunotherapy approved as a first-line agent for non-small cell lung cancer. However, this is just the beginning of the story, not the end.
Adapting the PD-L1 diagnostic to incorporate immune cell expression facilitated approval of pembrolizumab for several additional indications, and may shed light on the mechanism of action of checkpoint inhibitors
14:35 Detection and Characterization of Key Biomarkers in Immuno-Oncology
Rob Burgess, PhD, Sino Biological, Inc.
14:50 Innovation in Biomarker Driven Oncology
Clare Sarvary Fourrier, Senior Vice President, Clinical Operations – Europe, Precision for Medicine, Oncology and Rare Disease
Biomarkers
have created astonishing new opportunities for oncology research – from patient stratification to choice of MOA – helping realise the full potential of precision medicine. Yet, Biomarker-driven studies also present challenges. Innovations in Biomarker Driven Oncology, presented
by Clare Sarvary-Fourrier, Senior Vice President Precision for Medicine, Oncology and Rare Disease, offers much-needed insights into the evolving best practices around biomarker-driven studies. Topics include: successful delivery of bio-marker
driven studies; operationalising innovation; electronic data records and EDC connectivity.
15:05 Refreshment Break in the Exhibit Hall with Poster Viewing
15:45 Measuring Performance Status with Digital Tools: A Case Study in Metastatic Solid Tumors
Daniel R. Karlin, MD, MA, CEO, HealthMode, Inc.
Performance status is widely used to qualify patients for different treatment regimens or eligibility for clinical trials. The research-standard measures have low inter- and intraobserver agreement, low patient-clinician agreement, do not capture
low PO intake, lack subjectivity or an audit trail. Can a digital wearable and smart-phone passively and continuously collect activity data at sufficient coverage levels for analysis? We have run a feasibility study and there are some interesting
observations.
16:15 CO-PRESENTATION: Taking the Pain out of PD-L1 Scoring – Artificial Intelligence Supported IHC Quantification in Routine Diagnostics
Lukas Heukamp, MB, PhD, Director Molecular Pathology, Molecular Pathology, Institut für Hämatopathologie Hamburg
Felix Faber, CEO and Founder, MindPeak GmbH
Immunohistochemistry has become the core biomarker predicting response to novel Immuno-checkpoint Inhibitor therapies. Still, pathologist face a number of challenges in using PD-L1 IHC. Accurate quantification is cumbersome and requires extensive
training. In this talk, we present an AI method for IHC quantification including PD-L1 that supports pathologists in relevant scoring schemes. We have tested this method in a clinical setting with promising results for reproducibility, efficiency
and accuracy.
16:45 Novel Data Science Approaches for the Identification of Multivariate Biomarkers for Simultaneous Diagnosis of Multiple Cancer Diseases
Darius M. Dziuda, PhD, Professor, Mathematical Sciences, Central Connecticut State University
State-of-the-art data science methods are used in this project to search for characteristic gene expression patterns that are common for multiple cancer diseases. TCGA NGS data for several thousand patients, several tissues, and several tumor types
have been utilized. A parsimonious multivariate biomarker and – based on this biomarker – classifier of high sensitivity, specificity and accuracy of differentiating between the tumor and normal states have been identified.
17:15 Problem Solving Breakout Discussions (See complete list of Problem-Solving Breakout Discussion)
Why Digital Biomarkers?
Moderator: Daniel R. Karlin, MD, MA, CEO, HealthMode, Inc.
- What measurements are improved with digital tools?
- Better, Faster, More Robust? Sorting hype from reality in digital tools
- Regulatory aspects and challenges
Immunotherapies Beyond Melanoma and Lung Cancers
Moderator: Sheeba Irshad, MD, PhD, Senior Clinical Lecturer, Cancer and Pharmaceutical Sciences, Kings College London
- Strategies for converting cold tumours into hot tumours
- Coordinated clinical trial designs of immunotherapies
- Immunotherapy combinations
18:15 Dinner Short Course Registration
18:45 Dinner Short Course
Recommended Short Course*
Dinner SC3: Engineering of Bispecific Antibodies and Multi-Specific Non-Antibody Scaffolds - LEARN MORE
Mathieu Cinier, PhD, Scientific Director, Affilogic
Mattias Levin, PhD, Senior Scientist, Antibody Engineering, Alligator Bioscience AB
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THURSDAY 12 MARCH
8:00 Registration and Morning Coffee
8:30 Chairperson’s Remarks
Daniel R. Karlin, MD, MA, CEO, HealthMode, Inc.
8:35 Anti-PD-1 Monotherapy versus Combined Anti-PD-1 and Anti-CTLA-4 Immunotherapy in Metastatic Melanoma: Who Will Benefit?
Camelia Quek, PhD, Senior Scientist, Postdoctoral Scientist, Cancer Immunotherapy & Biomarkers, Melanoma Institute Australia
Immune checkpoint inhibitors including anti-PD-1 and anti-CTLA-4 have led to durable anti-tumour effects in patients with metastatic melanoma and other cancer types. However, approximately 60% of patients treated with immunotherapy fail to achieve
long-term durable response rates due either to failure to respond or to emergent drug resistance. A strong rationale for biomarker development that stratifies patients who might benefit from immune checkpoint inhibitors is urgently needed.
8:55 Quantifying Response and Characterizing Resistance to Neoadjuvant Anti-PD1 in Non-Small Cell Lung Carcinoma (NSCLC)
Tricia Cottrell, PhD, Assistant Professor, Pathology and Molecular Medicine,
Queens University
Neoadjuvant anti-PD-1 may improve outcomes for patients with resectable non-small cell lung cancer (NSCLC) and provides a critical window for examining pathologic features associated with response. Unique features of immune-mediated tumor
regression include immune activation, massive tumor cell death, and tissue repair. Multiplex immunofluorescence is a powerful new approach for characterizing the tumor immune microenvironment, both for biomarker and mechanistic discovery.
However, careful optimization and validation are warranted.
9:15 Proper Evidence Generation to Establish Clinical Values
Eugean Jiwanmall, MSc, MBA, Senior Research Analyst, Technology Evaluation & Medical Policy, INDEPENDENCE BLUE
CROSS
Understanding and developing per clinical needs are essential aspects during discovery of biologically & clinically relevant biomarkers. Getting these biomarkers to become part of routine clinical care is an exciting and fulfilling journey,
which should include a number of key pathways that must be anchored and supported by reliable evidence. Different phases from exploratory mechanisms to connecting biomarkers to therapeutic decisions require certain quantities and qualities
of evidence. States of evidence for biomarkers and therapies based upon them can evolve simultaneously or in sequence, but must cross certain thresholds to gain ubiquitous clinical usefulness. Having sufficient evidence for practical employment
of precision medicine’s tools and solutions is essential, and production of this evidence base is & will remain a necessity.
9:35 Validation of the ELISpot Assay for Primary Objectives
Vicky Sgouroudis, PhD, Associate Director, Scientific Team, Operations, Caprion Biosciences
The IFN-γ ELISpot is a powerful tool for the enumeration of antigen-specific T cell responses. The requirement for immunological assays in clinical trials to be rigorously validated has resulted in the validation of the ELISpot to ensure
precision, linearity, and to standardize the counting of the SFU for primary objectives. Validation parameters (precision, linearity, assay range, LOD) were evaluated. A non-biased statistical tool (DFR) was established to evaluate true
responses relative to vehicle control.
10:05 Coffee Break in the Exhibit Hall with Poster Viewing
10:15 Speed Networking in the Exhibit Hall
10:45 Chairperson’s Remarks
Roxana Dronca, MD, Associate Professor of Oncology, Consultant and Chair, Division of Hematology-Oncology, Mayo Clinic
10:50 Biomarkers of Response to Chemo-Immunotherapy in Metastatic Melanoma
Roxana Dronca, MD, Associate Professor of Oncology, Consultant and Chair, Division of Hematology-Oncology, Mayo Clinic
The mechanism responsible for the successful clinical outcomes of chemo-immunotherapy is not completely understood. We show that a subset of CD8+ T cells expressing the chemokine receptor CX3CR1 are able to withstand cytotoxic therapy and
their frequencies significantly increased in metastatic melanoma patients responding to paclitaxel/carboplatin with PD-1 blockade. The CX3CR1+CD8+ T cells have an effector memory phenotype and the ability to efflux chemotherapy drugs via
the ABCB1 transporter.
11:20 Peripheral T Cell Expansion Predicts Tumour Infiltration and Clinical Response
Jane Grogan, PhD, Chief Scientific Officer, ArsenalBio
Despite the resounding clinical success in cancer treatment by antibodies that block the interaction of PD-1 with its ligand PD-L1 [Mellman 2011], key unknowns remain concerning the mechanisms responsible. A major limitation to understanding
the origin and fate of T cells in tumor immunity is the lack of quantitative information on the distribution of individual T cell clonotypes in cancer patients. Here we performed deep single-cell sequencing of RNA and T cell receptors
(TCRs) in cancer patients across several indications, assessing the profiles of TCRs in the various populations of T cells in tumours, normal adjacent tissue (NAT), and peripheral blood.
11:50 KEYNOTE PRESENTATION: Challenges in Assessing the Efficacy of Immune-Oncology Drugs
Christophe Le Tourneau, MD, PhD, Senior Medical Oncologist, Department of Drug Development and Innovation (D3i), Institut
Curie, Paris, France
Due to their unique mechanism of action, immuno-oncology drugs display patterns of responses that are specific and sometimes challenging to handle in clinical practice. I will review these different patterns of response that include durable
responses, pseudoprogression, hyperprogression and dissociated responses, and provide some guidelines on how to handle them in the clinic.
12:20 Networking Lunch in the Exhibit Hall with Poster Viewing
13:05 Chairperson’s Remarks
Graham Pockley, PhD, CEO, multimmune GmbH; Professor of Immunobiology, John van Geest Cancer Research Centre, Nottingham Trent University
13:10 Membrane Hsp70 – A Novel Target for Isolating Circulating Tumour Cells
Graham Pockley, PhD, CEO, Multimmune GmbH; Professor of Immunobiology, John van Geest Cancer Research Centre, Nottingham Trent University
We provide evidence that a monoclonal antibody (mAb) against a membrane-bound form of Hsp70 (mHsp70) – cmHsp70.1 – can be used to isolate viable circulating tumour cells (CTCs) from peripheral blood of tumour patients. As the expression
of mHsp70 remains stably upregulated on migratory, mesenchymal CTCs, metastases and cells that have been triggered to undergo EMT, we propose that approaches based on capturing cells that express mHsp70 are advantageous over those based
on EpCAM expression.
13:40 FEATURED PRESENTATION: Leveraging Novel TCR/Antigen Discovery Technologies for (Pre)Clinical Applications
Wouter Scheper, PhD, Senior Postdoc, Molecular Oncology and Immunology, Netherlands Cancer Institute
There is a growing interest in trying to understand the cellular states of tumor-infiltrating T cells, for example using scRNAseq and high-dimensional mass cytometry. However, these technologies so far do not inform on the actual tumor-specificity
of intratumoral T cells. We have developed functional T cell receptor profiling platforms that allow the unbiased assessment of T cell specificities, and aim to leverage these technologies for developing next-generation TCR gene therapies.
14:10 Exploring the Ubiquitin Landscape in Immuno-Oncology
Adan Pinto-Fernandez, PhD, Postdoctoral Research Scientist, Nuffield Department of Medicine, University of Oxford
The deubiquitylating enzyme USP18 is a major negative regulator of the innate immune response, in particular of the modulation of the Interferon (IFN) signalling. USP18 is the only human enzyme that processes the Interferon stimulated
gene 15, ISG15, a ubiquitin-like protein tightly regulated in the context of innate immunity, in vivo. In this study we explored potential new roles of USP18 and ISG15 in Immuno-Oncology.
14:40 A Single-Cell View on the Tumour Immune Microenvironment
Jo Van Ginderachter, PhD, VIB Group Leader, Tumor-host interactions, Lab of Cellular and Molecular Immunology, VIB-Vrije Universiteit Brussel
The efficacy of cancer immunotherapy is suboptimal, at least partly due to the immunoregulatory capacity of tumor-infiltrating myeloid and lymphoid cell types, including tumor-associated macrophages, dendritic cells and regulatory T cells.
We investigated the ontogenic, molecular and functional heterogeneity of the tumor immune microenvironment by performing single-cell RNA-sequencing on mouse and human tumors in correlation with functional assays. We provide a detailed
insight in the complexity of this tumor compartment.
15:10 Close of Summit
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