Cambridge Healthtech Institute’s Inaugural

Biomarkers for Immuno-Oncology

Exploring Mechanisms of Predictive and Therapeutic Response

18-19 March 2019

 

Given the complexities in successfully modelling the heterogeneity of tumours and the human immune system preclinically, it is inherently difficult to develop accurate predictive biomarkers for cancer immunotherapy. Thankfully there is a significant effort across academia and industry to do just this. Employing cutting edge techniques such as genomics, transcriptomics, proteomics and metabolomics, as well as looking into more discreet blood niches, such as circulating tumour cells and exosomes, might just provide necessary the answers. At Cambridge Healthtech Institute’s Inaugural Biomarkers for Immuno-Oncology conference we will address this and more.

Final Agenda

MONDAY 18 MARCH

Recommended Short Course*

9:3012:30 SC1: The Tumour Microenvironment and Response to Cancer Immunotherapy - Detailed Agenda

*Separate registration required

12:30 Conference Registration

Biomarkers for Combinational Therapies

13:30 Organizer’s Welcome Remarks

Joel Hornby, BSc Hons, Conference Director, Cambridge Healthtech Institute

13:35 Chairperson’s Welcome Remarks

Helen Angell, BSc, PhD, MD, Principal Scientist, Translational Science, Oncology IMED Biotech Unit, AstraZeneca


13:45 FEATURED PRESENTATION: ctDNA as a Biomarker for Early Tumor Response Assessment in Lung Cancer Patients Treated with Immunotherapy

Ed Schuuring, MD, Head of the Laboratory of Molecular Pathology, Pathology, University Medical Center Groningen

A significant minority of patients treated with immune checkpoint inhibitors show durable responses, but no adequate biomarkers are available for predicting which patients will benefit. Immunotherapy is expensive and potentially toxic. Patient response is monitored by tumor volume using CT scanning. The aim of our study is to assess plasma KRAS/BRAF-mutant levels as an early biomarker and a monitoring tool for durable responses to immunotherapy in KRAS/BRAF-mutated advanced NSCLC.

14:15 Integrative Cancer Immunology: Clinical Translation of IO Biomarkers and the Immunoscore

Helen Angell, BSc, PhD, MD, Principal Scientist, Translational Science, Oncology IMED Biotech Unit, AstraZeneca

The Immunoscore, based on the quantification of lymphocytes and cytotoxic T cells at the tumour centre and invasive margin, is a clinically useful prognostic marker in colorectal cancer. The mechanistic relationship between tumour infiltrating immune cells and microsatellite instability will be presented. Translation of immune quantification into the clinic, evaluating additional indications and profiling the immune landscape of distinct molecular segments will be discussed.

14:45 Bim and Soluble PD-L1 as Biomarkers of Response to Anti-PD1 Therapy

Roxana Dronca, MD, Associate Professor of Oncology, Consultant and Chair, Division of Hematology-Oncology, Mayo Clinic

The dynamics and heterogeneity of programmed cell death protein ligand 1 (PD-L1) expression confound its use as a predictive biomarker in cancer immunotherapy, but blood-based biomarkers have the potential to predict responders and detect mechanisms of resistance to immunotherapy. We report that measurements of T cell biomarkers (Bim and effector memory) and sPD-L1 levels provide a new non-invasive way to predict and monitor patient responses to anti-PD-1 monotherapy in melanoma and lung cancers.

15:15 Networking Refreshment Break

15:45 Prognostic and Predictive Markers for Immunotherapy and Combination Therapy

Kathleen M. Mahoney, PhD, MD, Instructor of Medicine, Medicine, Hematology-Oncology, Beth Israel Deaconess Medical Center, Dana-Farber Cancer Institute

Many clinical trials have investigated the toxicity and efficacy of combining PD-1 pathway blockade with other therapies. Yet few randomized Phase II studies involving immune checkpoints have been designed to develop predictive biomarkers for these therapies. Biomarker-driven early phase trials are needed for designing Phase III trials to prospective validate (protein or gene signature-based) biomarkers for monotherapy or combination immunotherapy, which is necessary for expediting patients’ access of these therapeutic options.

16:15 Next-Generation Biomarkers for the Era of Combination Cancer Immunotherapy

Mohini Rajasagi, PhD, MD, Director Translational Oncology and Clinical Biomarkers, Oncology Clinical Research, Merck Sharpe and Dohme (MSD)

Immune checkpoint blockade therapies are revolutionizing the standard cancer treatment. Despite the current success of these therapies, not all patients respond to immunotherapy and even those that do often experience toxicities. Combination approaches are the keys to improving clinical response. From preclinical immune-oncology mouse models to patients enrolled in clinical trials, novel biomarkers and high throughput technologies enable us to understand the mechanisms underlying the complex interactions between the immune system and cancer, identify predictive biomarkers for the patients who will most likely benefit from current immunotherapies, avoid immune-related adverse events and guide future combination cancer immunotherapy.

16:45 Rapid High-Throughput Functional Selection of Neoantigens and Assessment of Their Safety

Milosevic Slavoljub, MD, Head of Technology and Innovation, Medigene AG

Neoantigens are an important class of highly specific target molecules for specific vaccine and TCR-based immunotherapies. Identification of neoantigens by next-generation sequencing and prediction of binding to the HLA allotypes of a patient still leaves open the issue of actual immunogenicity and safety of neoantigen targets for therapeutic use. Medigene combines high throughput functional screening with sophisticated in silico tools to overcome several current limitations in selecting relevant neoantigens.

17:15 Sponsored Presentation (Opportunity Available)

17:45 Welcome Reception in the Exhibit Hall with Poster Viewing

18:45 Close of Day

TUESDAY 19 MARCH

MONITORING IMMUNOTHERAPY RESPONSE

8:00 Registration and Morning Coffee

8:30 Chairperson’s Opening Remarks

Graham Pawelec, MA, PhD, FGSA, Professor of Experimental Immunology, Second Department of Internal Medicine, University of Tuebingen Clinical School, Germany; Affiliated Scientist, Cancer Solutions Program, Health Sciences North Research Institute, Canada

8:35 Aging and the Human Immune System in the Era of Immunomodulatory Antibody Therapy for Cancer: Is It All Downhill?

Graham Pawelec, MA, PhD, FGSA, Professor of Experimental Immunology, Second Department of Internal Medicine, University of Tuebingen Clinical School, Germany; Affiliated Scientist, Cancer Solutions Program, Health Sciences North Research Institute, Canada

It is “common knowledge” that the human immune system deteriorates over time, resulting in an increased frequency of and susceptibility to infectious disease, autoimmunity and cancer, and in poorer responses to vaccines in the elderly (immunosenescence). This presentation will consider the clinically highly relevant question of the impact of immune aging on the responses of cancer patients to immunomodulatory antibody therapy that is currently revolutionizing medical oncology (2018 Nobel Prize).

9:05 Immune-Stroma-Tumor Cell Interactions in Understanding Immune Blockade Drug Response

Jun Zhu, PhD, Professor, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai and Sema4, a Mount Sinai venture

Immune cell infiltration is positively associated with immune blockade drug response in general. However, high proportion of immune cell infiltration may not necessarily lead to good immune blockade drug response. We recently showed that immune and stroma cell interaction can predict PD-L1 response in bladder cancer (Wang et al, Nature Communications, 2018). Our single cell sequencing and computational modeling provide further insights of how immune-stroma-tumor cell interactions can determine immune blockade drug response.


9:35 Problem Solving Roundtable Discussion

Biomarkers to Predict Response and Toxicity to Immunotherapy

Moderator: Roxana Dronca, MD, Associate Professor of Oncology, Consultant and Chair, Division of Hematology-Oncology, Mayo Clinic

10:35 Coffee Break in the Exhibit Hall with Poster Viewing

11:15 Systems Approach to Cancer Immunology Biomarker Discovery

Matthew Albert, MD, PhD, Principal Scientist, Cancer Immunology, Genentech

Germline genetic polymorphisms influence tumor gene expression and immune cell infiltration.


 

11:45 Applying Immune Receptor Sequencing in the Discovery and Profiling of Immuno-Oncology ‘Living Drugs’

Jan H. Bergmann, PhD, MD, Senior Scientist, Genomics Platform Technologies and Immune Receptor Discovery, AgenTus Therapeutics

Recent developments in sequencing technologies both on bulk and in particular the single cell level open up tremendous opportunities in functional immune receptor discovery, preclinical R&D as well as treatment monitoring in the field of immuno-oncology. Collectively, genomics technologies paired with innovative cell and molecular strategies are leveraging increased sensitivity and specificity to complement this rapidly developing therapeutic field.

12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:45 Dessert Break in the Exhibit Hall with Poster Viewing

13:15 Session Break

THE MICROBIOME AND METABOLOMIC BIOMARKERS

14:00 Chairperson’s Remarks

Tina J. Hieken, MD, FACS, Associate Professor of Surgery, Surgery, Mayo Clinic

14:05 The Breast Tissue Microbiome, Stroma and Immune Cells in Association with Benign and Malignant Breast Disease

Tina J. Hieken, MD, FACS, Associate Professor of Surgery, Surgery, Mayo Clinic

Stromal changes, as well as alterations in the immune cell composition of benign breast lobules, encompassing both innate and adaptive immune effectors, have been described in association with future breast cancer risk. In tandem, pilot data suggests that the composition of the innate microbiome of sterilely obtained histologically normal breast tissues is different between women with and without breast cancer. Associations between the breast tissue microbiome, microenvironment and disease state (benign versus malignant) suggest potential novel biomarkers of breast cancer risk and targets for primary prevention.

14:35 Multiplexing of Tryptophan and Its Metabolites for Patient Stratification and Monitoring in Immuno-Oncology

Christiane Opitz, PhD, Group Leader, Brain Cancer Metabolism, German Cancer Research Center, DKFZ

Tryptophan degradation is a potent immunosuppressive mechanism regulating anti-tumor immune responses. As treatments modulating tryptophan degradation are becoming available, methods to efficiently and precisely measure tryptophan degradation are becoming increasingly relevant both for stratification of patients to treatments as well as assessment of therapeutic efficacy. We employed isobaric mass tags to develop a method that enables quantitative comparison of tryptophan degradation simultaneously in up to 11 different samples. Using this method we studied the effects of the tryptophan pathway modulator indoximod on tryptophan metabolism in human cancer and immune cells. A proof of principle study comparing tryptophan degradation in 40 glioblastoma patients to age- and sex-matched healthy controls revealed reduced levels of tryptophan and downstream tryptophan metabolites in the glioblastoma patients.

15:05 Sponsored Presentation (Opportunity Available)

15:35 Refreshment Break in the Exhibit Hall with Poster Viewing

TRANSLATIONAL BIOMARKERS AND SUCCESS IN THE CLINIC

16:15 Omic Insights into Immune Resistance Mechanisms

Jim Eyles, PhD, Principal Scientist, Translational Medicine (Oncology), MedImmune

16:45 The First Biomarker-Defined Tumor Indication: FDA Approval of Pembrolizumab for MSI-High Cancer

Kenneth Emancipator, DABP, MD, Executive Medical Director and Head of Companion Diagnostics, Translational Medicine, Merck & Co.

The program presents an overview of microsatellite instability (MSI) and mismatch repair defect (dMMR), and how it fits into the tumor immunogenicity-inflammation pathway. It reviews the history and clinical evidence for MSI and dMMR as a predictive biomarker for response to pembrolizumab. It discusses the unprecedented – and unorthodox – path to FDA approval of pembrolizumab. Finally, it discusses MSI and dMMR in the broader context of biomarkers in immuno-oncology.

17:15 Biomarkers for the Translation of a Novel Small Molecular Immunomodulatory Therapy

Stephanie Traub, PhD, Biomarker Development Specialist, Drug Development Center, Cancer Research UK

17:45 Close of Biomarkers for Immuno-Oncology