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

WEDNESDAY 11 MARCH

PLENARY KEYNOTE SESSION

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

CLINICAL BIOMARKERS AND COMPANION DIAGNOSTICS

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 Sponsored Presentation (Opportunity Available)

15:05 Refreshment Break in the Exhibit Hall with Poster Viewing

DIGITAL BIOMARKERS, AI, ML, AND DATA SCIENCE FOR IO

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

PD-L1 immunohistochemistry has become the core biomarker predicting response to novel immuno-checkpoint inhibitor therapies for advanced cancer patients. Still, pathologists face a number of challenges in using PD-L1 IHC on a daily basis. Different treatments require different quantification and scoring systems across several tumor entities. In addition, routine diagnostics has its own set of challenges like variances in slide preprocessing and staining. Furthermore, accurate quantification is cumbersome, time consuming and requires extensive training.

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 Roundtable Discussions

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

THURSDAY 12 MARCH

8:00 Registration and Morning Coffee

PREDICTIVE MARKERS, BIOMARKERS OF RESPONSE AND PRECISION MEDICINE

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.

9:05 Novel Patterns of Response to Immunotherapy

Edith Borcoman, MD, Medical Oncologist, Institut Curie, Paris

9:35 Sponsored Presentation (Opportunity Available)

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

10:15 Speed Networking in the Exhibit Hall

PREDICTIVE MARKERS, BIOMARKERS OF RESPONSE AND PRECISION MEDICINE (CONT.)

10:45 Chairperson’s Remarks

Bruno Gomes, DVM, PhD, Head of Oncology Biomarkers, Early Clinical Development Oncology, Roche Pharma Research and Early Development

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

11:20 Opportunities and Challenges for Biomarkers in Early Clinical Development in IO

Bruno Gomes, DVM, PhD, Head of Oncology Biomarkers, Early Clinical Development Oncology, Roche Pharma Research and Early Development

The presentation will present the opportunities and challenges in developing impactful biomarker strategies for early clinical development of new immuno-oncology drugs. We will focus on the design of fit-for-purpose entry into human clinical trials, proof or dis-proof of mechanism of action and optimal biological dose finding.

11:50 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.

12:20 Networking Lunch in the Exhibit Hall with Poster Viewing

ADDRESSING THE TUMOUR MICROENVIRONMENT

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

Benedikt Kessler, PhD, Professor of Biochemistry and Life Science Mass Spectrometry, Nuffield Department of Medicine, University of Oxford

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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