Cambridge Healthtech Institute’s Second Annual

Immuno-Oncology Biomarkers 2: Immune Profiling and Immune Monitoring

June 12-13, 2018 | Westin Boston Waterfront | Boston, MA

Advances in immuno-oncology promise to revolutionize cancer treatment. However, many patients do not respond to immunotherapy. Immune profiling promises to identify biomarkers that predict response to immunotherapy and help monitor its progress. Cambridge Healthtech Institute’s Second Annual Immuno-Oncology Biomarkers 2: Immune Profiling and Immune Monitoring meeting will cover quantitative approaches to assess the state of the immune system, profile the tumor microenvironment and peripheral blood, determine tumor mutational burden and profile neoepitopes, and develop predictive and response biomarkers.

Final Agenda

Tuesday, June 12

12:15 pm Conference Registration

almac12:55Luncheon Presentation: Diagnostic Solutions for Multi-Arm I-O Clinical Trials

Steven Walker, PhD, Head, Internal Product Management, Almac Diagnostics

During this talk participants will learn about Almac Diagnostics’: - Novel strategy for patient stratification in Basket & Umbrella trials - Solution to enable multiple biomarkers to be evaluated from one sample - Cancer panel solutions for both DNA & RNA - Unique product offering for Immuno-Oncology - Customised patient reporting enabling simple interpretation of molecular data.

1:25Session Break

 

MICROSATELLITE INSTABILITY AND MISMATCH REPAIR DEFICIENCY BIOMARKERS

1:55 Chairperson’s Opening Remarks

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

2:00 Biomarkers for Mismatch Repair Deficiency in Cancer

Robert A. Anders, MD, PhD, Associate Professor, Pathology; Co-Director, Tumor Microenvironment Center, Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University

2:30 The First Biomarker-Defined Tumor Indication: FDA Approval of Pembrolizumab for MSI-High Cancer

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

The program presents an overview of microsatellite instability (MSI) and mismatch repair defect (MMRD), and how it fits into the tumor immunogenicity-inflammation pathway. It reviews the history and clinical evidence for MSI and MMRD 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 MMRD in the broader context of biomarkers in immuno-oncology.

3:00 The Power of Single Molecule Counting (SMC™): The Future of Immunoassays

Anitaben Tailor, PhD, SMC Technology & Application Advancement Lead, Research & Development, MilliporeSigma

Single Molecule Counting (SMC™) uses the power of high definition technology to help accelerate biomarker research. Data generated with customers demonstrates picogram to femtogram quantification limits applicable to low abundance biomarkers. With the SMCxPro® Immunoassay System, even the smallest changes in biomarker levels can be measured, allowing researchers to gain unprecedented insights into complex disease, drug efficacy and drug safety.

3:30 Refreshment Break in the Exhibit Hall. Last chance for poster viewing.

 

TUMOR MICROENVIRONMENT PROFILING

4:25 Chairperson’s Remarks

Marios Giannakis, MD, PhD, Medical Oncologist & Clinical Investigator, Dana-Farber Gastrointestinal Cancer Treatment Center; Researcher, Broad Institute of MIT and Harvard

4:30 Genetic Mechanisms of Immune Evasion in Colorectal Cancer

Marios Giannakis, MD, PhD, Medical Oncologist & Clinical Investigator, Dana-Farber Gastrointestinal Cancer Treatment Center; Researcher, Broad Institute of MIT and Harvard

We molecularly characterized 1,211 colorectal cancers (CRCs) and demonstrated that WNT-signaling and immune-related genes are significantly mutated in CRC. We also showed immuno-editing in microsatellite-instability high (MSI-H) tumors through biallelic antigen-presentation machinery mutations. In both microsatellite stable and MSI-H CRCs, we used transcriptional and immunohistochemical orthogonal analyses to demonstrate exclusion of an effective immune infiltrate through an active WNT-signaling pathway. These results can inform novel immunotherapy trials in CRC patients.

5:00 Leveraging RNA Expression Profiling to Direct Evaluation into Complex Tumor-Immune Associations

Darrell R. Borger, PhD, Scientific Director, Immuno-Profiling Laboratory; Director, Translational Research/Biomarker Laboratory, Massachusetts General Hospital Cancer Center

The complexity of the tumor-immune environment is underscored by the diversity of cell types, signaling processes, and secreted factors that can modulate how a patient responds to immunotherapy. This talk will highlight integration of RNA expression profiling to identify relevant immune escape mechanisms, cytokine pathway activation, and infiltrating immune signatures. Together with MSI testing and multispectral imaging, specific targetable immune signatures across cancer types will be presented.

5:30 The Immune Microenvironment of Neoplastic Precursor Lesions

Elizabeth Thompson, MD, PhD, Assistant Professor, Pathology and Oncology, The Johns Hopkins University School of Medicine

While much work has focused on the tumor immune microenvironment of established cancers, little is known about the immune response to the earliest stages of tumor development. This talk will explore the immune microenvironment of neoplastic precursor lesions using ductal and lobular carcinoma in situ of the breast and pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm of the pancreas as models.

6:30 Dinner Short Course*

SC3: Multiplexed Analysis of Tumor Tissues Using Spatially Resolved and Quantitative Platforms

*Separate registration required

Wednesday, June 13

7:25 am Interactive Breakout Discussion Groups with Continental Breakfast

This session features discussion groups that are led by a moderator who ensures focused conversations around the key issues listed. Attendees choose to join a specific group, and the small, informal setting facilitates sharing of ideas and active networking. Details on the topics and moderators are available on the conference website.

INTEGRATED BIOMARKER ANALYSIS FOR PRECISION IMMUNO-ONCOLOGY

8:25 Chairperson’s Remarks

Andrey Loboda, PhD, Director, Genetics and Pharmacogenomics, Merck

8:30 Paired and Dynamic Multiplex Analyses of Tissue Markers for Biomarker Discovery

Sacha Gnjatic, PhD, Associate Professor, Tisch Cancer Institute, Hematology/Oncology, Immunology, Icahn School of Medicine at Mount Sinai

With immunotherapy rapidly becoming standard of care for a variety of tumor types, including non-small cell lung, head and neck, and urothelial carcinoma, the new frontier is to understand mechanisms and identify biomarkers that explain why so many patients still fail to experience clinical benefit. The study of immune recognition of tumors is therefore of central importance, not only as a baseline measurement of immunocompetence that may be harnessed by immunomodulatory drugs, but also as a predictive biomarker of response with dynamic changes over time. Some of the most interesting biomarkers so far are based on intrinsic tumor immunogenicity, including cancer/testis antigens and neoantigens, as well as presence of a variety of immune cells that recognize these antigens or modulate immunity at the tissue site. Through development of novel high-dimensional approaches to investigate the tumor microenvironment in unprecedented depth, with the help of single cell techniques and dedicated deep-learning data analysis tools, a composite picture of the tumor microenvironment should help map the complexity of factors interacting locally that collectively have personalized prognostic or predictive value.

9:00 Integrating Data from High-Throughput, High-Content Platforms for Informative MOA Analysis of Single Agent and Combination Immunotherapies in Preclinical Models

Gerald Hall, PhD, Principal Research Scientist, Experimental and Translational Immuno-Oncology: Biomarkers, Eli Lilly

The use of biomarkers in preclinical immuno-oncology is critical for comprehensive hypothesis testing and generating insightful new MOA hypotheses in early preclinical development. The use of multiple integrated high-throughput, high-content cellular and molecular platforms, as well as model systems, allows for the interrogation of biological processes involved in drug treatment and generation of novel ideas regarding MOA, off target effects, and rational drug combinations.

9:30 Getting Closer to the Picture and Data for Immuno-Oncology Assays Using the Celigo Image Cytometer

Leo Chan, Technology Research & Development Manager, Nexcelom Bioscience LLC

Immuno-oncology assays are conducted by release assays, but can be inaccurate due to indirect supernatant measurement. We demonstrated the detection of antibody/cell-mediated cytotoxicity in 2D/3D models using the Celigo. The image cytometer could analyze live cells to measure time/dose-dependent cytotoxicity. The proposed method can perform high-throughput cancer drug screening.

Personalis9:45 Tumor Immunogenomic Profiling: High-Content Assays and Analytics

Christelle Johnson, MS, PhD, Senior Field Applications Scientist, Cancer Genomics & Immuno-Oncology, Personalis, Inc.

Few platforms support multidimensional biomarker analysis. This talk will highlight ACE ImmunoID™ as a universal platform for biomarker discovery that enables comprehensive variant detection, neoantigen identification, and characterization of tumor immunogenomics. We will feature a case study demonstrating the platform’s ability to identify tumor escape mechanisms for cancer immunotherapy.

10:00 Networking Coffee Break

10:30 Molecular Mechanisms and Biomarkers Predictive of Response to Keytruda

Andrey Loboda, PhD, Director, Genetics and Pharmacogenomics, Merck

The talk will address molecular biomarkers of response to pembrolizumab, including the role of tumor antigenicity, as measured by mutational load (ML) and T cell inflamed microenvironment in predicting the response to pembrolizumab. Data will be presented that prospectively validates the utility of both biomarkers as tumor type agnostic and orthogonal measures of response. These findings provide a biomarker framework for development of pembrolizumab as a monotherapy and for characterizing responses to novel immunotherapy regimens.

11:00 Precision Immunology through Deeper Single-Cell Profiling

Pratip Chattopadhyay, PhD, Associate Professor, Pathology; Director, Precision Immunology Incubator, Isaac and Laura Perlmutter Cancer Center, New York University Langone Medical Center

Three trends have dominated biomedical research over the last decade. The first, the NIH Roadmap’s Single Cell Analysis Program, was founded on the principle that cells are extremely heterogenous, and that this heterogeneity is important in health and disease. For this reason, cells must be characterized individually, rather than by insensitive and misleading analysis of bulk cell populations. This trend renewed appreciation for cellular heterogeneity, and incited a revolution of new technologies that could comprehensively analyze single cells (the second trend, deep profiling). Finally, a third biomedical research trend was sparked by President Obama’s Precision Medicine Initiative, which aims to define genomic and proteomic differences between patient groups, and use this information to inform treatment decisions. In this talk, I will discuss my work at the intersection of these three trends, and demonstrate the value of new technologies for comprehensive and complete cellular analysis. I will provide examples of how deep knowledge about immune responses can be attained, using examples drawn from our recent work in immunotherapy and fundamental immunology. This talk will highlight our work developing 30 parameter flow cytometry, single-cell RNA sequencing, CITE-Seq (for simultaneous measurement of protein and transcripts), and new bioinformatic tools.

11:30 Integrative Analyses of Environment, Microbiota, and Tumor Immunity Can Inform Immuno-Oncology Research

Shuji Ogino, MD, PhD, Professor (Pathology & Epidemiology), Brigham & Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Harvard T.H. Chan School of Public Health; Associate Member, Broad Institute of MIT and Harvard

The integrative field of “immunology-MPE” (molecular pathological epidemiology) is an emerging paradigm, and can investigate influences of the exposome (dietary, lifestyle, environmental, microbial, pharmacological, and other exposures) on tumor-immune interactions, thereby informing immunotherapy research. Using over 1,000 colorectal cancer cases with rich data on immune response, whole exome sequencing (tumor and normal DNA), tumor neoantigens, and clinical outcomes, proof-of-principle immuno-MPE studies have shown great promise for precision prevention and immuno-oncology.

PerkinElmer NEW 200912:00 pm Luncheon Presentation: Enabling Multidimensional Translational Data Management & Analysis for Biomarkers Discovery and Patients Stratification

Eduardo Gonzalez, Bioinformatics Product Strategist, Informatics, PerkinElmer

In this presentation, we will show how domain experts, like oncologists, can directly gain insight by exploring and analyzing complex translational datasets in a rich visual environment connected to the Cloud. Advanced analytics for biomarker discovery facilitate self-service data exploration to empower scientists using embedded, well-established analytics, allowing the direct exploration and analysis of complex datasets—including omics data—to progress biomarker projects.

 

IMMUNE MONITORING: BIOMARKERS OF RESPONSE AND RESISTANCE

1:25 Chairperson’s Remarks

1:30 Response and Resistance in CAR-T Therapy

Elena Orlando, PhD, Bioinformatics Investigator, Novartis Institutes for Biomedical Research

2:00 Molecular Determinants for Sensitivity and Resistance to Immunostimulatory Therapies in Cancer

Kurt Schalper, MD, PhD, Assistant Professor, Pathology and Medicine (Medical Oncology), Yale School of Medicine

2:30 Cancer Immunotherapy Biomarkers for Selection and Monitoring

Glen J. Weiss, MD, MBA, Director, Phase I Clinical Research, Beth Israel Deaconess Medical Center, Boston

There are now multiple monoclonal antibody immunotherapies available for clinical use to treat advanced cancers. However, just a fraction of these patients experience an impressive durable response. How are these therapies selected and how is efficacy monitored? This lecture will highlight current data on biomarkers being used and evaluated for treatment selection and monitoring.

3:00 Close of Conference