Cancer immunotherapy research continues to charge forward at a rapid pace. There have been advances in existing technologies, mounting research in target discovery, and better understanding of molecular mechanisms. Still, much work needs to be done before immunotherapies are ready for standard use and biomarkers will play a pivotal role. Cambridge Healthtech Institute’s Second Annual Biomarkers for Cancer Immunotherapy will showcase research on both predictive and prognostic biomarkers while addressing the biggest questions around predictors of immune response. Focus will be given to clinical trial case studies, global vs. type-specific markers, and molecular mechanisms. Overall, this event will provide solutions to bridge the gap between biomarkers and therapy selection.
Final Agenda
Thursday, March 10
7:30 am Registration and Morning Coffee
8:30 Chairperson’s Opening Remarks
Scott Rodig, M.D., Ph.D., Hematopathologist, Department of Pathology, Brigham and Women’s Hospital
8:40 Combination Therapies with Listeria-Based Immunotherapies: From Chemotherapy to Checkpoint Inhibition
Dirk G. Brockstedt, Ph.D., Senior Vice President, Research & Development, Aduro Biotech, Inc.
This talk will give a detailed description of Listeria-based immunotherapy. It will also review clinical studies in mesothelioma, pancreatic and ovarian cancer. Lastly, it will share results of combination studies with conventional chemotherapy, cell-based therapies and immune modulators.
9:10 Biomarkers for Prediction of Response to Anti-Cancer Immunostimulatory Therapies: Where Are We?
Kurt A. Schalper, M.D., Ph.D., Director, Translational Immuno-oncology Laboratory (T.I.L.)., Yale Cancer Center
Monoclonal antibodies targeting the co-inhibitory immune checkpoint PD-1 or its primary ligand PD-L1 are well tolerated and can induce lasting clinical responses in patients with advanced malignancies. However, the majority of patients treated with such agents do not receive clear benefit, highlighting the need for companion biomarkers to select subjects with the highest potential of response. Current status and recent developments in biomarkers for immunostimulatory therapies will be discussed.
9:40 The Role of Global Immunocompetence in Cancer Immunotherapy
Holden Maecker, Ph.D., Associate Professor, Microbiology and Immunology; Director, Human Immune Monitoring Center, Stanford University
In order to cast a broad net in measuring potential parameters of immunocompetence, we have stimulated patient PBMC with PMA+ionomycin and then analyzed their cell phenotypes and functions using a 40-parameter mass cytometry panel. We combine this with a serum Luminex assay for 63 cytokines. Results from different tumor types and different immunotherapy settings will be presented. We wish to determine whether there are broadly applicable immunocompetence measures as well as those that are unique to a given tumor and/or therapeutic setting.
10:10 The Emergence of icScore™as a Novel Immune-Based Approach for Monitoring Cancer Patients
Henry Hepburne-Scott, Ph.D., Director, Business Development, Serametrix
• Cancer immunotherapies offer great promise but some patients fail to respond
• Immune-based biomarker assays can help predict clinical response to this emerging drug class
• Serametrix has developed icScoreTM, an immune monitoring system designed for cancer patients
10:25 Blood-Based Cancer Immunotherapy Diagnostics
Heinrich Roder, Ph.D., Chief Technology Officer, Research & Development, Biodesix
Blood-based clinically-actionable, multivariate tests from MALDI ToF data can be designed by modifying ideas from deep learning. Our methodology utilizes time-to-event endpoints in generating training labels. Results for a test stratifying patients for immunotherapy benefit will be shown.
10:40 Coffee Break with Exhibit and Poster Viewing
11:15 Defining the Immune Landscape in Cancer Using Spatially Resolved Approaches
Paul C. Tumeh, M.D., Assistant Professor, Medicine, University of California, Los Angeles
Immunodiagnostics, aimed at comprehensively defining the immune system’s response to tumors, must be able to capture two biological hallmarks of immune cell types, i) plasticity and ii) lack of mutations. Spatially resolved approaches that are capable of high molecular content profiling and multiparametric analysis have the ability to define previously unknown spatiotemporal interdependencies that would deepen our understanding of how the immune system responds to tumors before and after immunotherapy.
11:45 Tissue-Based Analyses to Guide Immunotherapy for Lymphoma
Scott Rodig, M.D., Ph.D., Hematopathologist, Department of Pathology, Brigham and Women’s Hospital
Targeted immunotherapy has achieved long-lasting clinical responses in a subset of patients with a variety of aggressive malignancies. I will discuss the cellular and molecular characteristics of classical Hodgkin lymphoma that render this tumor-type uniquely susceptible to PD-1 blockade and correlations between tissue-based biomarker analysis and clinical outcome with either conventional chemotherapy or immunotherapy, and extensions of these observations to additional lymphoma subtypes.
12:15 pm Leveraging Ultrasensitive Immunoassay Technology to Drive New Research and Clinical Insights in Immuno-Oncology
Mark Roskey, Ph.D., Vice President and General Manager, Quanterix
12:30 Session Break
12:40 Luncheon Presentation (Sponsorship Opportunity Available)
or Enjoy Lunch on Your Own
1:50 Chairperson’s Remarks
Brad Nelson, Ph.D., Director, Deeley Research Centre, BC Cancer Agency
2:00 PD-1 Blockade in Tumors with Mismatch-Repair Deficiency
Luis Diaz, M.D., Associate Professor, Oncology, John Hopkins Kimmel Cancer Center
Somatic mutations have the potential to encode “non-self” immunogenic antigens. Tumors with a large number of somatic mutations due to mismatch-repair defects appear to be highly susceptible to immune checkpoint blockade. This presentation will summarize the clinical and genomic data of using mutations as neoantigens.
2:30 Prognostic and Predictive Markers for Immunotherapy and Combination Therapy
Kathleen M. Mahoney, M.D., Ph.D., Clinical Instructor, Beth Israel Deaconess Medical Center; Research Fellow, Dana Farber Cancer Institute
Tumor expression of PD-L1 has received much attention as a potential biomarker for PD-1/PD-L1 directed therapy. However it is inappropriate as a biomarker for exclusion from treatment, since “PD-L1 negative” tumors may respond to PD-1 pathway blockade. Emerging data suggests multivariate models including PD-L1 expression and the immune infiltrate within the tumor microenvironment may direct immunotherapy decisions. Incorporating the tumor’s mutational landscape, in addition to immunohistochemistry and gene expression signatures, may improve these platforms.
3:00 Refreshment Break with Exhibit and Poster Viewing
3:30 PANEL: Moving Forward with Prognostic Biomarkers for Immunotherapy
Moderator: Luis Diaz, M.D., Associate Professor, Oncology, John Hopkins Kimmel Cancer Center
Panelists: Bernard A. Fox, Ph.D., Harder Family Chair for Cancer Research, Member & Chief, Laboratory of Molecular & Tumor Immunology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer Center, Providence Portland Medical Center; CEO, UbiVac
Kurt A. Schalper, M.D., Ph.D., Director, Translational Immuno-oncology Laboratory (T.I.L.)., Yale Cancer Center
Brad Nelson, Ph.D., Director, Deeley Research Centre, BC Cancer Agency
- Status updates on immune biomarkers
- Validation of new biomarkers
- Technologies and high throughput approaches – strengths and weaknesses
- Investigating the tumor microenvironment
4:00 Imprime PGG – An Advanced, Clinical Stage Pathogen Associated Molecular Pattern (PAMP)
Jeremy R. Graff, Ph.D., CSO & Senior Vice President, Research, Pharmaceutical Group, Biothera, Inc.
Imprime PGG is a yeast beta glucan PAMP- Pathogen Associated Molecular Patterning molecule. As a PAMP, Imprime enlists the functionality of the innate immune system to trigger a coordinated immune response to cancer. Imprime enhances the anti-tumor efficacy of tumor-targeting, anti-angiogenic and immune checkpoint inhibitor antibodies. To date, Imprime has completed multiple phase 2 clinical studies and has been safely administered to more than 400 subjects. Importantly, Imprime activity requires the formation of an immune complex with anti-beta glucan antibodies (ABA). Accordingly, levels of these ABA differ in the human population and may delineate those most likely to respond to Imprime-based therapy.
4:30 Genomic Approaches to Deciphering Protective Immune Mechanisms in Cancer
Brad Nelson, Ph.D., Director, Deeley Research Centre, BC Cancer Agency
Tumor-infiltrating lymphocytes are associated with survival in virtually every human cancer studied, but the mechanisms by which they confer protective immunity remain incompletely understood. Focusing on ovarian cancer, our group applies genomic and molecular pathology approaches to define the mechanisms by which the immune system responds to the evolving tumor genome over space and time. We are translating these insights into clinical trials involving adoptive transfer of tumor-reactive T-cells.
5:00 Reception with Exhibit and Poster Viewing
6:00 Close of Day
Friday, March 11
8:00 am Morning Coffee
8:25 Chairperson’s Remarks
Bernard A. Fox, Ph.D., Harder Family Chair for Cancer Research, Member & Chief, Laboratory of Molecular & Tumor Immunology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer Center, Providence Portland Medical Center; CEO, UbiVac
8:30 Immunotherapy at a Tipping Point: DPV-001 – A DC-Targeted Strategy with More than 100 Cancer Antigens, Multiple TLR Agonists and Damps Induces Broad-Spectrum Anti-Cancer Immunity in Patients with Cancer
Bernard A. Fox, Ph.D., Harder Family Chair for Cancer Research, Member & Chief, Laboratory of Molecular & Tumor Immunology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer Center, Providence Portland Medical Center; CEO, UbiVac
Cancer immunotherapy is providing objective responses in patients with many cancers. Unfortunately, response rates are low and most regressions are not complete. One hypothesis to explain these results is that only patients with immunity against a spectrum of antigens, expressed on highly heterogeneous metastases, obtain a complete, and potentially curable, response. A Phase II trial is testing the ability of DPV-001, a DC-targeted micro-vesicle, to induce broad anti-cancer immunity.
9:00 Cancer Immunotherapy Biomarkers: Lessons from Clinical Trials
Lisa H. Butterfield, Ph.D., Professor, Medicine, Surgery and Immunology; Director, UPCI Immunologic Monitoring and Cellular Products Laboratory, University of Pittsburgh
There is a critical need for the identification, standardization and validation of biomarkers for cancer immunotherapy. Predictive and prognostic biomarkers are needed to focus therapies on those able to benefit. While many candidates have been identified in clinical trials, there are technical issues with measurements and biomarkers correlate in some settings and diseases and not others. This presentation will discuss recent trials, candidate biomarkers and the SITC Biomarkers Taskforce initiative.
9:30 Product Characteristics and Pharmacodynamic Biomarker Profile of Patients Receiving Anti-CD19 CAR T Cell Therapy: Correlates of Clinical Response
Margo Roberts, Ph.D., CSO, Kite Pharma, Inc.
Anti-CD19 chimeric antigen receptor (CAR) engineered autologous T-cell therapy has shown promising efficacy in an ongoing Phase I study in the setting of B-cell malignancies conducted at the NCI. In a Kite Pharma-sponsored Phase I - II multi-center study, ZUMA-1, subjects received KTE-C19: autologous T-cells engineered with the same anti-CD19 CAR construct as the NCI utilizing an optimized 6 - 8 day process. Potential correlates of clinical response to KTE-C19 will be presented, including KTE-C19 product composition, anti-CAR T-cell expansion profile and serum pharmacodynamic markers.
10:00 Bringing the Next Generation of Immuno-oncology Biomarkers to the Clinic: Opportunities and Challenges
Alessandra Cesano, M.D., Ph.D., CMO, NanoString Technologies
The role of the immune system in the cancer patient outcome has been now fully recognized and the importance of biomarkers in guiding therapeutic strategies is clear. Because of the complexity of the immune response and of the tumor biology, the current FDA-approved (for use of checkpoint inhibitors in NSCLC) single-analyte biomarkers (i.e., PD-L1 IHC assays) are only minimally informative. There is a need for new biomarkers to measure and integrate the complexity of host, tumor, and environment based on measurement of different molecular entities, i.e., DNA, RNA, and proteins. The ability to simultaneously measure multiple types of analyte from a single sample maximizes the amount and type of information we get per sample. In the presentation, new approaches to biomarker discovery and development in immune-oncology based on the nCounter® Analysis system will be discussed.
10:30 Coffee Break with Exhibit and Poster Viewing
11:00 Moderator’s Remarks
James R. Mansfield, Global Head, Imaging, Quantitative Pathology Solutions, PerkinElmer
11:05 Establishing a PD-L1 Companion Diagnostic for Opdivo, a Novel Immune Checkpoint Inhibitor for the Treatment of Cancer
Steven D. Averbuch, M.D., Vice President, Development, Oncology & Pharmacodiagnostics,
Bristol-Myers Squibb
PD-L1 expression on the membrane surface of solid tumors may correlate with the efficacy of PD-1 pathway inhibitors. Nivolumab is a fully human IgG4 PD-1 immune checkpoint inhibitor antibody that selectively prevents interaction with PD-L1 and PD-L2 to inhibit the suppression of antitumor T-cell function. A comprehensive analytical and clinical evaluation of PD-L1 expression by IHC to determine the association between expression and clinical outcome for Nivolumab will be described.
11:20 A Critical Appraisal of Biomarkers for Immune Therapy: The Pathologist’s Perspective
Robert A. Anders, M.D., Ph.D., Associate Professor, Pathology, Johns Hopkins School of Medicine; Director, Liver Pathology, Division of Gastrointestinal and Liver Pathology, Johns Hopkins Hospital
Dr. Anders will summarize the current understanding of immune checkpoint inhibitors. The mechanism of action of check point inhibitors targeting PD-1/PD-L1 and CTLA will be the focus of the discussion. Particular emphasis will be on gastrointestinal malignancies. He will discuss the challenges in developing prognostic and predictive biomarkers in patient derived tissues.
11:35 Developing an Immunohistochemistry Test for “Programmed Cell Death 1 Ligand” (PD-L1) as a Companion Diagnostic for Pembrolizumab
Kenneth Emancipator, M.D., Executive Medical Director, Molecular Biomarkers and Diagnostics, Merck Research Laboratories
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.
11:50 PANEL DISCUSSION
12:30 pm Close of Symposium