As pharmaceutical and biotechnology companies increase their investment in immuno-oncology programs to facilitate rapid development of novel immunotherapies, there is increasing pressure to discover and validate relevant biomarkers. Cambridge Healthtech Institute’s Second Annual Immuno-Oncology Biomarkers meeting will bring together biomarkers experts from industry and academia to address rapid development of predictive and prognostic IO biomarkers, utility of these biomarkers in clinical trials, and their potential as companion diagnostics.
Final Agenda
Monday, May 1
12:00 - 5:00 pm Short Course Registration and Conference Pre-Registration
1:00 - 4:00 Short Course*
SC1: Fit-for-Purpose Biomarker Assay Development and Validation
5:00 - 8:00 Dinner Workshop*
SC2: Liquid Biopsy for Immuno-Oncology and Precision Medicine
5:00 – 8:00 Dinner Short Course*
SC3: Preparing for Companion Diagnostic Device Studies and Submissions to FDA
*Separate registration required
Tuesday, May 2
7:00 am Conference Registration and Morning Coffee
8:00 Chairperson’s Opening Remarks
Nicholas C. Dracopoli, Ph.D., Vice President, Oncology Diagnostics, Janssen Research & Development
8:10 Immuno-Oncology Companion Diagnostics Development: A Complex Systems Approach
Lourdes Barrera, Ph.D., Global Capability Director, Diagnostics, AstraZeneca
Development of companion diagnostics for emerging immunotherapies is more complicated because they are not dependent on driver mutations in the drug target. Consequently, we need to develop new biomarker strategies for the development of immunotherapies. During this review, we will give some examples of how complex systems approach is supporting the development of new biomarkers and potentially companion and complementary diagnostic tests.
8:35 The Evolution of Oncology Companion Diagnostics from Signal Transduction to Immuno-Oncology
Nicholas C. Dracopoli, Ph.D., Vice President, Oncology Diagnostics, Janssen Research & Development
Companion diagnostic (CDx) tests for signal transduction inhibitors measure the activation status of the drug target. CDx tests for immune modulating drugs will be much more complicated and need to measure the immune status of tumors and differentiate those with a suppressed immune response from those with no prior immune response. These new CDx tests will drive the choice of therapeutic intervention with checkpoint inhibitors or alternative approaches to prime a new immune response.
9:00 An Industry Perspective on Clinical Biomarkers and Companion Diagnostics for Checkpoint Inhibitor Therapies
Arnold B. Gelb, M.D., MS, FASCP, FCAP, Senior Director, Global Clinical Biomarkers and Companion Diagnostics, EMD Serono
Ongoing trends in clinical oncology support the value proposition of using a precision medicine approach for patient selection and enrichment strategies when developing immuno-oncology therapeutics. This presentation will review aspects pertinent to checkpoint inhibitor therapies of exploratory analyses of clinical biomarkers to identify predictive/prognostic clinical biomarkers that may lead to co-development of a companion diagnostic or a complementary diagnostic. Examples will be drawn from the current status of approved PD-L1 assays, citing the limitations thereof, and other clinical biomarkers and candidate companion or complementary diagnostics, including characterizations of the tumor microenvironment, immune cell phenotyping, T cell repertoires, IFN-gamma gene signature, neoantigen burden/mutational load, microsatellite instability status, and potentially other “hot topics” such as liquid biopsies.
9:25 Coffee Break in the Exhibit Hall with Poster Viewing
10:10 Chairperson’s Remarks
Nicholas C. Dracopoli, Ph.D., Vice President, Oncology Diagnostics, Janssen Research & Development
10:15 RNA, DNA or Protein? Or All Three? Development of Multiple Diagnostics Predicting Response to Pembrolizumab
Matt Marton, Ph.D., Director, Genomics and Companion Diagnostics, Translational Biomarkers, Merck
An effective diagnostic strategy for anti-PD1 therapy may require multiple predictive biomarkers that assess the complexity of both tumor biology and the immune system. In addition to PD-L1 protein expression, multiple biomarkers, including gene expression and mutation burden, have been proposed as predictors of response to anti-PD1 therapy. We will discuss analytical performance characteristics of potential diagnostic devices under development, including an RNA-based gene expression device being studied in multiple indications.
10:40 Precision Medicine and IO Biomarkers
Jean-Marie Bruey, Ph.D., Companion Diagnostics Group Leader, Genentech
The past decade has witnessed a revolution in our understanding of the immune system and our ability to develop safer and more effective immunotherapies. Classification of diseases according to their biological underpinnings will guide more precise targeting of new therapies, and molecular/biomarker characterization of therapeutic responses will provide direction for therapy improvement. The PD-1/PD-L1 checkpoint inhibitors are important contributions in finding more effective treatments against cancer, and it is likewise important that we have companion diagnostics available that will guide treatment.
11:05 Enabling Immuno-Oncology Based Development through Image-Based Cell Sorting to Recover Pure Cell Populations from Complex Patient Tumor Tissue Specimens
Farideh Bischoff, Ph.D., Chief Clinical Development Officer, Menarini Silicon Biosystems
Ana Paula Da Silva, Ph.D., Senior Scientist, Menarini Silicon Biosystems
Tumor infiltrating lymphocytes (TILs) are biomarkers that play a critical role in cancer, including differential diagnosis, determination of prognosis, treatment response, and disease progression. However, analysis of gene expression in fresh tissue may not accurately depict the gene profile as it can change aggressively during lymphocyte isolation and RNA extraction. In this presentation, we demonstrate the use of the DEPArray™ platform to isolate pure populations of lymphocytes from fixed mouse tissue for downstream RNA analysis.
11:35 Enabling Companion Diagnostic Development for Challenging Biomarkers with RNAscope: A Quantitative In Situ RNA Biomarker Platform
Robert Monroe, M.D., Ph.D., CMO, Advanced Cell Diagnostics, Inc.
Recent advances have made RNA ISH an attractive platform for companion diagnostics. RNA ISH now has the ability to detect RNA expression in automated, chromogenic assays at the single cell level in histological sections, allowing for biomarker assessment by diagnosticians at the light microscope. This presentation will review how RNA ISH addresses various issues with IHC and other CDx platforms and how it is being used in CDx development for a variety of challenging biomarkers.
12:05 pm Session Break
12:15 Luncheon Presentation: Simoa for the Ultra-Sensitive Measurement of Proteins as Biomarkers of Immuno-Oncology Therapeutics
Mark Roskey, Ph.D., Vice President and General Manager, Quanterix
We will describe the use of single molecule arrays (Simoa) to measure proteins that are emerging as important biomarkers for the effectiveness of immuno-oncology therapies. Immune-targeted therapies, e.g., checkpoint inhibitors, have emerged as the next generation approaches to treating cancer.
1:30 Chairperson’s Remarks
Ann Kapoun, Ph.D., Vice President, Translational Medicine, OncoMed Pharmaceuticals
1:35 The New Precision Medicine: The Role of Dynamic Tumor and Immune Sampling in Immunotherapy
Morganna Freeman, D.O., Medical Oncologist, Immunotherapeutics, The Angeles Clinic and Research Institute
Immunotherapy has revolutionized the oncology treatment landscape, and as therapies evolve, there is a recognized need for biomarkers to inform the likelihood and duration of response. Radiologic assessments, i.e. RECIST, may be supplanted by biologically relevant markers in order to develop timely, cost-effective, and potentially personalized therapy. This presentation will review dynamic tumor and immune sampling as early markers of clinical response and their emerging role in clinical decision making.
2:00 Developing Biomarker Strategies for Immuno-Oncology
Ann Kapoun, Ph.D., Vice President, Translational Medicine, OncoMed Pharmaceuticals
This presentation will cover: precision medicine in IO, challenges to developing biomarkers preclinically in the IO space, and examples of clinical applications.
2:25 An RNA-Based Immunophenotyping Assay; Robust Tumor Microenvironment Characterization from a Single RNA Isolation
Jarret Glasscock, Ph.D., CEO, Cofactor Genomics, Inc.
Immune recognition, activation, and infiltration are all required for effective clearance of a tumor by the immune system. Impairment of tumor avoidance mechanisms each requires a different therapeutic strategy. We have developed Paragon to provide a comprehensive profile of a tumor’s microenvironment, including measurement of the expression levels of immune checkpoint genes, quantification of the total mutational burden of the tumor, and levels of infiltration of multiple immune cell subtypes; from a single RNA sample.
2:55 Refreshment Break in the Exhibit Hall with Poster Viewing
3:45 Biomarker Considerations in Early Phase Immunotherapy Clinical Trials
Lucy Xu, Ph.D., Associate Director, Biomarker Development Support & Global Health, hhc Data Creation Center, Eisai
The recent successes in immuno-oncology have been attained with immune checkpoint blockade, targeting T-lymphoid cell-based immunosuppressive mechanisms. Despite success with checkpoint inhibitor monotherapies, some patients develop resistance. Successful integration of the large body of new data from the translational science disciplines, including biomarkers, is critical. As a case study, a novel first-in-class immunotherapy drug targeting myeloid immunosuppressive mechanisms and clinical biomarker approaches used will be discussed.
4:10 Rational Biomarker Development for Checkpoint Inhibition in Colon Cancer
Robert Anders, M.D., Ph.D., Associate Professor, Pathology, Johns Hopkins University
Cancer samples can be used to predict response to treatment. For example, patients whose breast cancer samples express HER2/neu may be treated with and respond to HER2 blockade. Recently PD-L1 expression has been touted as a predictive biomarker for immune therapy. While PD-L1 does have some predictive power, it is not a perfect biomarker. A better approach for developing predictive biomarkers is to integrate genomic, protein and immunologic markers. When this strategy is applied to patients with colorectal cancer, it is possible to select over 90% of patients that are likely to show a biologic response to anti-PD-1/L1 therapy. This lecture will cover ideas of integrating multiple platforms to predict who will respond to therapy.
4:35 Identifying Immune Biomarkers for Treatment Prognosis and Response in Genitourinary Malignancies
Susan F. Slovin, M.D., Ph.D., Attending Physician, Member, Genitourinary Oncology Service, Sidney Kimmel Center for Prostate and Urology Cancers, Memorial Sloan Kettering Cancer Center; Professor, Medicine, Weill Cornell Medical College
The identification of novel immune-based biomarkers that can portend treatment response or change in a cancer’s biology remains a major imperative for clinical trials with immunologic agents. Controversy exists from clinical trial to clinical trial for a specific malignancy with regard to the up- or down-regulation of checkpoint markers such as PD-1 and PD-L1, and their association with clinical benefit, thereby making it difficult to assess their role as biomarkers. The potentials and pitfalls of using immune biomarkers will be discussed with relevance to current successful Phase II and Phase III trials for genitourinary cancers.
5:00 Welcome Reception in the Exhibit Hall with Poster Viewing
5:30 Short Course and ThinkTank Registration
6:00 - 9:00 pm Dinner Short Course*
SC4: Next-Generation Sequencing as a Clinical Test
6:00 - 9:00 pm Dinner ThinkTank*
SC5: PD-L1 Assays for Biomarkers and Companion Diagnostics
*Separate registration required
Wednesday, May 3
7:30 am Morning Coffee
7:55 Chairperson’s Remarks
Michael J. Overman, M.D., Associate Professor, Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center
8:00 Immune-Profiling Platforms for Biomarker Discovery in Immune-Oncology
Ignacio I. Wistuba, M.D., Professor & Chair, Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center
The discovery of new molecules and pathways with pivotal functions regulating the immune system facilitated the emergence of new cancer treatments and the investigation of novel biomarkers to predict response. The development of these biomarkers requires the participation of immunology, pathology and genomics. We developed a translational molecular pathology immune-profiling platform to discover and validate biomarkers in tissue and fluids for immune-oncology in clinical samples from patients in clinical trials.
8:25 NGS Solutions Across IO Drug Development: From Biomarker Discovery to IVD
John Simmons, Ph.D., Director, Translational Science and Diagnostics, Personal Genome Diagnostics
Personal Genome Diagnostics is a next-generation sequencing (NGS) company that collaborates with Bio-Pharma to support biomarker discovery and diagnostic development with assays using both tissue (FFPE) and plasma (ctDNA) inputs. Here we will discuss applications of our core technologies, including whole exome sequencing (WES), neoantigen prediction, RNA-Seq, targeted ctDNA panels, tumor mutational burden (TMB), and microsatellite instability (MSI) assays relevant to the IO space.
8:55 Immune Monitoring of Cancer Vaccines and Immunotherapy: What Have We Learned and Where to Go Next?
Sacha Gnjatic, Ph.D., Associate Professor, Tisch Cancer Institute, Hematology/Oncology, Immunology, Icahn School of Medicine at Mount Sinai
With clinical success of cancer immunotherapy, it is essential to understand the mechanisms of novel drugs by measuring their effect on immune cells, in the periphery and at the tumor site. Novel approaches and technologies are needed to address the complex task of identifying biomarkers of clinical activity and to improve the design of future therapies.
9:20 Biomarker Strategies for Cancer Vaccine Trials
Stephanie Traub, Ph.D., Biomarker Specialist, Centre for Drug Development, Cancer Research UK
Recent developments in the PD-1 field have shown promising progress in combination of checkpoint inhibitors and cancer vaccines. However, one critical point that hasn’t been answered yet, which is probably the initial pitfall of cancer vaccines, is the question of how an effective immune response should look and how this immune response can be monitored.
9:45 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 The Evolving Role of Immune Checkpoint Therapy in Colorectal Cancer with and without Deficient Mismatch Repair
Michael J. Overman, M.D., Associate Professor, Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center
Immune checkpoint therapy targeting PD-1/PD-L1 has shown robust activity in colorectal cancer with mismatch deficiency or microsatellite instability (MSI-high) but not microsatellite stable (MSS) colorectal cancer. It is now clear that MSI-high cancers represent a unique molecular tumor subset that should be approached with immune-based therapy. This talk will discuss the current combinatorial efforts within MSI-high colorectal cancer and also the emerging combinations that are being explored in MSS colorectal cancer.
11:10 Somatic Alterations in HLA Genes as an Immune Escape Mechanism in Cancer
Sachet A. Shukla, Ph.D., Senior Scientist, Dana-Farber Cancer Institute
Mutations in HLA genes, which are located in the most polymorphic region of the genome, are difficult to characterize and may profoundly affect the efficacy of many immunomodulatory therapies. Computational analyses strongly suggest acquisition of HLA mutations to be an adaptive response to immunological pressure in many different tumor types. Lack of somatic alterations in HLA genes may therefore be a useful patient selection criterion in immunotherapeutic clinical trials.
11:35 Combinatorial Therapeutic Strategies for Ovarian Cancer
Yvonne Lin, Ph.D., Associate Medical Director, Product Development, Oncology, Genentech-Roche
Ovarian cancer remains the leading cause of death among all gynecologic cancers. Recent advances in understanding molecular profiles of ovarian cancer have led to incorporating targeted therapies into the treatment plan. Characterization of an immunoreactive subtype of ovarian cancer supports pairing immune checkpoint inhibitors with ovarian cancer therapies to deliver highly effective therapy for patients.
12:00 pm Immunohistological and Genomic Correlations and Differences Between Various Anti-PD-L1 Clones
Maher Albitar, M.D., Senior Vice President, CMO and Director, Research and Development, NeoGenomics Laboratories
Expression of PD-L1 protein as detected by immunohistochemistry is commonly used for selecting patients for immunotherapy. Multiple assays using different antibody clones are currently used. Current research is focused on exploring if genomic abnormalities can be used for better selection of patients for immunotherapy. Furthermore, as combination therapy is being planned, there is a need to correlate immunotherapy biomarkers with targeted therapy biomarkers. This presentation will discuss the correlation between genomic abnormalities and the various PD-L1 immunohistochemistry assays.
12:30 Close of Conference