Recent advances in cancer immunotherapy have generated excitement across all fields of oncology. When working, immune checkpoint inhibitors, cancer vaccines and adoptive T-cell therapies create more sustainable results with less probability of recurrence than conventional or targeted cancer therapy. But can we predict when it will work and do we know how to monitor patients’ response? According to Dr. Ira Mellman (Genentech), “both patient selection and the discovery of new therapeutic opportunities will be dependent on the ability to identify, collect and understand biomarkers and immunobiology of patient response and lack of response”. Challenges in discovering predictive biomarkers for cancer immunotherapy are very significant and include multiple cell types involved, multiple mechanisms of T cell regulation, genetic heterogeneity of tumors and immune components, etc. Many industry and academia researches are fighting these odds right now and they would definitely benefit from a productive discussion. Cambridge Healthtech Institute’s inaugural Diagnostics to Guide Cancer Immunotherapy conference is designed to bring together clinical immuno-oncologists, researchers from pharmaceutical and biotech companies and members of laboratory medicine community to discuss the need and underlying mechanism of cancer immunotherapy biomarkers as well as the existing and emerging assays aiming to improve patients outcomes.

WEDNESDAY, AUGUST 19

10:30 am Registration

1:25 Refreshment Break in the Exhibit Hall with Poster Viewing

DIAGNOSTICS TO GUIDE IMMUNOTHERAPY BEYOND GENOMICS

1:50 Chairperson’s Opening Remarks

Stephen Johnston, Ph.D., Co-Director, The Biodesign Institute, Innovations in Medicine, Professor College of Liberal Arts and Sciences, School of Life Sciences, Arizona State University

2:00 KEYNOTE PRESENTATION: Diagnostics to Guide Immunotherapy Beyond Genomics

Sam M. Hanash, M.D., Ph.D., Professor, Molecular Pathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center

Understanding the mechanisms of immune evasion exhibited by tumor cells is essential for effective immunotherapy. Defining these mechanisms extends beyond genomic characterization of tumors and requires elucidation of dynamic processes of altered metabolism and altered protein expression, localization, processing and presentation of antigens, leading to diagnostics to guide immunotherapy.

2:30 Deciphering The Diagnostic Landscape for PD-1/PD-L1 Checkpoint Inhibitors

Marcin Kowanetz, Ph.D., Biomarker Lead for Atezolizumab (anti-PDL1), Oncology Biomarker Development, Genetech
Cancer immunotherapies provide long lasting and durable responses in patients. To identify patients who best respond to these therapies, development of diagnostic strategies become important particularly as more drugs enter clinical trials over the next decade. Emerging clinical data on PD-L1 as a predictive marker of monotherapy checkpoint inhibitors in NSCLC and UBC will be presented. Lastly, biomarkers that aid the rational development of combination strategies will be reviewed.

3:00 Companion Diagnostics for Immune-Based Treatments of Cancer: The Role of Immunohistochemical Methods

Clive R. Taylor, M.D., Ph.D., Professor, Chairman of the Department of Pathology, USC Keck School of Medicine, Los Angeles

Personalized medicine demands personalized pathology. Molecular, genomic and immunohistochemical (IHC) techniques have demonstrated the value of Companion Diagnostics’ in classifying patients as ‘responders’ or ‘non-responders’ for targeted therapies, including immune based therapies. Many of the targets for immunotherapy are proteins and IHC is, in theory, the ideal method for their detection and measurement. This presentation addresses challenges that growing demand for quantitative Companion Diagnostics present for IHC.

3:30 Q&A with Speakers

4:00 Refreshment Break in the Exhibit Hall with Poster Viewing

4:45 Development of an Immunohistochemistry Test for “Programmed Cell Death 1 Ligand” (PD-L1) as a Companion Diagnostic for Pembrolizumab

Marisa Dolled-Filhart, Ph.D., Director, Pathology and Companion Diagnostics, Molecular Biomarkers and Diagnostics, Clinical Flow Cytometry and Molecular Pathology, Merck & Co., Inc.

Tumors express PD-L1 to contribute to escape from immunosurveillance. Pembrolizumab blocks this escape mechanism and thus effectively treats a number of cancers. The rapid clinical development of pembrolizumab required rapid development of an immunohistochemistry assay for PD-L1. Merck developed the assay initially to determine whether or not PD-L1 is a predictive biomarker, then to enrich clinical trials, and ultimately partnered with a diagnostics company to develop the assay as a companion diagnostic

5:15 Biomarkers as Guide Posts in Patient Selection and Process Development of Chimeric Antigen Receptor-Directed T Cell Therapy

J. Joseph Melenhorst, Ph.D., Director, Product Development & Correlative Sciences Labs, Translational Research Program, Pathology and Laboratory Medicine; Adjunct Associate Professor, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania

T cells equipped with chimeric receptors (CAR) targeting tumors have evolved rapidly from a basic scientific tool to a new way in which we induce remission in patients with very poor risk cancer. The synergy between basic and translational science continues to further boost the utility of immunotherapy and enhance its potency in various forms of cancer. In my talk I will highlight recent developments in the field and conclude with how correlative studies may contribute to the success of this therapy.

5:45 Immunosignatures to Detect and Treat Cancer Early

Stephen Johnston, Ph.D., Co-Director, The Biodesign Institute, Innovations in Medicine, Professor College of Liberal Arts and Sciences, School of Life Sciences, Arizona State University

Immunosignatures is a simple method to profile the antibodies in an individual. This platform diagnostic may be useful for diagnosing any disease, including cancer. It could be applied to stratify potential recipients of ICIs or to follow the course of response to treatment. We have also examined the ability of IMS to detect cancer at early stages. We will present data from mouse model on combining early detection with early ICI treatment.

6:15 Close of Day

6:00 Dinner Short Course Registration

THURSDAY, AUGUST 20

PROGRAMMED CELL DEATH 1 LIGAND AND BEYOND

8:25 Chairperson’s Opening Remarks

David L. Rimm, M.D., Ph.D., Yale University

8:30 Measuring Immune Checkpoint Targets

David L. Rimm, M.D., Ph.D., Professor, Pathology, Executive Director, Translational Pathology, Director, Yale Pathology Tissue Services, Yale University

Immune checkpoint therapies, specifically PD-L1 axis drugs, are extremely promising showing durable response in high stage patients. However, they are effective on only a small percentage of the population; about 10-30% depending on tumor type. The assays to identify these patients has been challenging. Here we describe antibodies and assays that have been used to measure PD-L1 expression and also examine other variables that may help to predict response to therapy.

9:00 Adaptive Immune Resistance by Tumor: Biomarker Implications

Janis Taube, M.D., Assistant Professor, Departments of Dermatology and Pathology, Johns Hopkins School of Medicine

Immune resistance by tumor may have both adaptive and constitutive components, and both have mechanistic and biomarker implications. This talk will discuss our ongoing efforts to characterize further the local tumor microenvironment with the aim of improving patient selection and developing rational treatment combinations to overcome adaptive immune resistance.

9:30 Selected Poster Presentations:

Molecular Characterization of Sipuleucel-T Using Whole Genome mRNA ProfilingHarini Kandadi, Senior Computational Biology Analyst, Dendreon – Valeant Pharmaceuticals

Molecular Deconstruction and Cellular Enumeration of the Tumor Microenvironment in Triple-Negative Breast CancerSunitha Sastry, Ph.D., Senior Product Manager, Cellecta, Inc.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

10:50 PD-L1 Assays in Lung Cancer

Fred R. Hirsch, M.D., Ph.D., Professor, Medicine and Pathology, University of Colorado Cancer Center; CEO, International Association for the Study of Lung Cancer (IASLC)

Immunotherapy for patients with advanced NSCLC has emerged as a very promising therapeutic avenue. Clinical studies indicate that patients with PDL-1 expressing tumors have a better response than those with PDL-1 negative tumors. Several companies are pursuing PDL-1 assays, but they all seem to be different in terms of defining a PDL-1 positive tumor. The International Association for the Study of Lung Cancer (IASLC) is planning an international characterization study of the PDL-1 assays in order to get a better understanding of the comparability between the assays and their performance on different types of specimens (large specimens, small biopsies, cytology) and different platforms.

11:20 Principles of Checkpoint Blockade in Gastrointestinal Malignancies

Robert Albert Anders, M.D., Ph.D., Associate Professor, Pathology, Johns Hopkins School of Medicine

Patient tissue has been tied to patient prognosis since Cuthbert Duke’s famous 1932 classification of colorectal cancer. The American Joint Committee on Cancer Tumor/Nodes/Metastases system refined and replaced the Dukes classification of colorectal cancers. Current efforts based upon the quality, quantity and location of the immune response to malignancy may provide more prognostic information. The development of immune check point inhibitors will be discussed in the setting of gastrointestinal cancers.

11:50 MDSC Clinical Assay as a New Diagnostic for Cancer

Alan L. Epstein, M.D., Ph.D., Professor, Pathology, University of Southern California, Keck School of Medicine

Myeloid derived suppressor cells have been found to correlate with tumor burden in thyroid and prostate cancer and may offer clinicians a new assay to assess tumor growth in patients undergoing treatment. The assay consists of a panel of three monoclonal antibodies used with flow cytometry on blood samples taken at the time of diagnosis or during therapy. Additional clinical trials in renal, bladder, and breast cancer are in progress.

12:20 pm Sponsored Presentation (Opportunity Available)

12:50 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:20 Session Break

2:00 Chairperson’s Remarks

Sriram Sathy, Ph.D., Director, Target and Biomarker Discovery, Jounce Therapeutics

2:05 Developing a Multi-Parametric Approach For Biomarkers And Patient Enrichment Strategies In Immune-Oncology

Sriram Sathy, Ph.D., Director, Target and Biomarker Discovery, Jounce Therapeutics

Clinical proof of concept has been demonstrated with agents such as anti-CTLA-4 and anti-PD-1. This success was facilitated by greater understanding of the mechanisms of the immune mediated tumor escape, including the role that T cell checkpoint inhibitors play in this process. Jounce is focused on developing cancer immunotherapies that are geared to provide durable clinical responses through identification of optimal targets for specific indications and for certain subsets, patients within those indications. Towards this goal we have developed a robust translational platform that allows for both target identification as well as patient/indication selection in an unbiased fashion. This approach relies on the fundamental principle of defining the immune system content and characteristics via a comprehensive multiple parameters approach. The talk will focus on multiple biomarkers that needs to be examined in the clinic to associate with response and explore available methodologies to address these biomarkers in the clinic.

2:35 Prediction of PD-1 Blockade Response by Adaptive Immune Resistance

Paul Tumeh, Ph.D., CSO, Dermatology, Acteris, Inc.

Measurement of pre-existing CD8+ T cells distinctly located at the invasive tumor margin have been shown to reliably predict response to therapies targeting the PD-1/PD-L1 immune inhibitory axis. Moreover, tumor regression after therapeutic PD-1 blockade requires pre-existing CD8+ T-cells that are negatively regulated by PD-1/PD-L1-mediated adaptive immune resistance. This presentation will review the clinical analysis of patients with metastatic melanoma obtained before and during anti-PD-1 therapy (pembrolizumab) using quantitative immunohistochemistry and quantitative multiplex immunofluorescence.

3:05 Uncovering Rational Candidates for Novel Immuno-Oncological Therapies

Scott Rodig M.D., Ph.D., Pathology, Brigham & Women’s Hospital and Dana-Farber Cancer Institute, Associate Professor, Pathology, Harvard Medical School

PD1 blockade using human antibodies elicits potent anti-tumor immunity in a subset of patients with cancer. Novel agents targeting a broad array of additional immuno-modulatory proteins are now in early stage clinical trials for patients with advanced disease. We will describe the development and application of novel quantitative methods to identify and quantify critical immunological markers in tissue biopsy samples that serve to facilitate the selection of tumor types and patient populations that are most likely to benefit from specific, targeted immuno-therapies.

3:35 PANEL DISCUSSION: Enabling Immune Checkpoint Inhibitors Therapy

Moderator: David L. Rimm, M.D., Ph.D., Professor, Pathology; Executive Director, Translational Pathology, Director, Yale Pathology Tissue Services, Yale University

• Discover novel immune checkpoints as antibody targets for cancer immunotherapy
• Validate predictive biomarkers
• Design and validate clinical assay

4:05 Close of Conference