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

Irshad_SheebaSheeba 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

Emancipator_KennethKenneth 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

Michael_BurgessRob Burgess, PhD, Sino Biological, Inc.


PrecisionForMedicine_Oncology 14:50 Presentation to be Announced

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

Karlin_DanDaniel 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

heukamp_lukasLukas 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

Dziuda_DariusDarius 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

Why Digital Biomarkers?

Karlin_DanModerator: 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

Irshad_SheebaModerator: 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

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 QuekCamelia 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)

Cottrell_TriciaTricia 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 JiwanmallEugean 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 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_DroncaRoxana 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 Opportunities and Challenges for Biomarkers in Early Clinical Development in IO

Gomes_BrunoBruno 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 KEYNOTE PRESENTATION: Challenges in Assessing the Efficacy of Immune-Oncology Drugs

Christophe-Le-TourneauChristophe 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

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

Pockley_GrahamGraham 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 KesslerBenedikt 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

Van_Ginderachter_JoJo 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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