Personalized Immunotherapy Header

Fueled with advances in genomic technologies, personalized oncology promises to innovate cancer therapy and target previously undruggable space. Developments in personalized cancer vaccines, adoptive T-cell therapies, as well as biomarker-driven immuno-oncology clinical trials, are enabling the next generation of cancer therapy. Cambridge Healthtech Institute’s Second Annual Personalized Immunotherapy meeting brings together clinical immuno-oncologists and thought leaders from pharmaceutical and biotech companies, and leading academic teams to share research and case studies in implementing patient-centric approaches to using the immune system to beat cancer.

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

5:008:00 Dinner Short Course*

SC3: Preparing for Companion Diagnostic Device Studies and Submissions

*Separate registration required

Tuesday, May 2

7:00 am Conference Registration and Morning Coffee

 

Companion Diagnostic Development in Immuno-Oncology

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

 

Neoantigen-Targeted Therapies

10:10 Chairperson’s Opening Remarks

Philip M. Arlen, M.D., President & CEO, Precision Biologics

10:15 Monoclonal Antibodies Targeting Novel Immunogenic Neo-Epitopes for the Treatment of Solid Tumors

Philip M. Arlen, M.D., President & CEO, Precision Biologics

Immunogenic neoantigens were derived from a membrane preparation of pooled allogeneic colorectal cancer and screened for immunogenicity. The immunogenic fraction was used as a vaccine for chemotherapy refractory disease and a positive correlation was observed in patients who developed antibody responses to therapy. Using this vaccine as a platform, monoclonal antibodies were developed and characterized that were sensitive and specific to cancer, not normal cells, and demonstrated antitumor activity.

10:40 Turning Tumor Mutations into Personalized Cancer Therapies

Roman Yelensky, Ph.D., Executive Vice President, Sequencing and Bioinformatics, Gritstone Oncology

Tumor-specific neo-antigens (TSNAs) can be targeted by the immune system. Gritstone Oncology is exploiting this tumor vulnerability in a therapeutic immunization strategy. The approach includes NGS to identify candidate TSNAs, proteomics and machine learning to predict which TSNAs can activate T cells, the manufacture of a personalized TSNA-based vaccine, and delivery in a combination regimen.

11:05 In silico Discovery of Gene Fusion Neoantigens for Personalized Cancer Immunotherapy

Christopher Maher, Ph.D., Assistant Professor, Department of Medicine, Division of Oncology, Washington University

Studies have used NGS to discover tumor specific neoantigens. However, these analyses have relied on somatic missense mutation-based neoantigen discovery workflows, thereby missing gene fusions that may translate into a novel immunogenic peptide. To address this critical gap, we developed INTEGRATE-Neo for gene fusion neoantigen discovery using NGS data and demonstrate its utility for discovering novel personalized cancer immunotherapy targets.

11:30 High-Throughput Generation of Neoantigen-Specific T Cell Receptors for Adoptive T Cell Therapy

Markus Dangl, Ph.D., Senior Vice President, Research & Pre-Clinical Development, Medigene AG

TILs specific for neoantigens and tumors with high mutational loads underlie effective immunotherapies. Questions remain whether neoantigens are good targets only for highly mutated tumors and patients with pre-existing neoantigen-specific T cells. Medigene uses its immunotherapy platform technologies to investigate neoantigens as future targets for vaccine and adoptive T cell therapies.

11:55 Session Break

 Quanterix12:15 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.

 

Personalized Cancer Vaccines

1:30 pm Chairperson’s Remarks

Joshua Brody, M.D., Director, Lymphoma Immunotherapy Program, Icahn School of Medicine at Mount Sinai

1:35 In situ Vaccination: Potential Mechanism(s) of Action and Biomarker Development

Robert Pierce, M.D., Scientific Director, Immunopathology Core, Fred Hutchinson Cancer Research Center

In situ vaccines (ISVs), intratumoral therapies that aim to enhance tumor immunogenicity, offer the potential to generate tumor antigen-specific TIL and augment anti-PD1 blockade. Multiple ISVs are in clinical development, including TLR agonists, STING agonists, oncolytic viruses and proinflammatory cytokines. ISVs offer a potential safety advantage due to relatively low systemic exposure and may be useful in combination with systemic immunotherapies. Mechanism of action-based biomarker development will be discussed.

2:00 In situ Vaccination to Potentiate Checkpoint Blockade Therapy

Joshua Brody, M.D., Director, Lymphoma Immunotherapy Program, Icahn School of Medicine at Mount Sinai

We have developed a novel in situ vaccine, in an animal model and in patients with low-grade lymphoma, combining: 1) Flt3L to recruit DC, 2) radiotherapy (XRT) to load DC with tumor-associated antigens (TAA), and 3) toll-like receptor agonist (TLRa) to activate TAA-loaded DC for cross-presentation. Strikingly, we observed partial and complete systemic tumor regressions, improving months after therapy, and even elimination of malignant B cells with sparing of healthy B cells, all suggesting a systemic anti-tumor immune response. Pre-clinical studies show similar results and enhancement with PD1 blockade. These data have motivated a new trial of the combination therapy which should compel future trial designs to consider optimizing cross-presentation to maximize the potential of checkpoint blockade therapy.

2:25 Playing the Numbers Game: Driving High-Titer T Cell Responses to Tumor Neoantigens

Raphael Rousseau, M.D., Ph.D., CMO, Gritstone Oncology

2:55 Refreshment Break in the Exhibit Hall with Poster Viewing

3:45 Immunotherapy for Prostate Cancer: Challenges and Opportunities

Marijo Bilusic, M.D., Ph.D., Associate Research Physician, National Cancer Institute, National Institutes of Health

The efforts are underway to develop better and more targeted therapies for prostate cancer. The first therapeutic cancer vaccine which demonstrated survival advantage in metastatic castration-resistant prostate cancer while maintaining an excellent quality of life was sipuleucel-T, approved in 2010. With several novel agents in clinical development, immunotherapeutics will likely continue to play an important role in the treatment of prostate cancer.

4:10 Development of Commercially Viable Private Neoantigen-Based Vaccines

Agnete Fredriksen, Ph.D., CSO, Vaccibody

Increasing evidence supports the role of neoantigens as promising targets of anti-tumour responses. However, development of commercially viable private neoantigen vaccines faces many challenges. Vaccibody is combining the attractive rapid, robust and cost-effective manufacturing of individual DNA vaccines with a unique mechanism of action of the encoded Vaccibody fusion protein that ensures efficient immune responses through attraction, activation and antigen loading of APC, and will pursue clinical trials in 2017.

4:35 Th1-Selected Epitope-Based Vaccination as the Lynchpin for Cancer Immunotherapy Combinations

William Watt, Ph.D., President & CEO, EpiThany

The proliferation of targets and molecules for immunomodulation of the tumor microenvironment highlights the need for a new vaccine approach to generate reliable anti-tumor immune responses for modulating. Decades of investment in vector and adjuvant technologies have achieved modest progress in the diversity and immunogenicity of self-antigen cancer vaccines. On a new platform, EpiThany is developing a pipeline of Th1-selective MHCII epitope-based vaccines as the lynchpin for emerging immune-oncology combinations.

5:00 Welcome Reception in the Exhibit Hall with Poster Viewing

5:30 Short Course and ThinkTank Registration

 

6:00-9:00 Dinner Short Course*

SC4: Next-Generation Sequencing as a Clinical Test

6:00-9:00 Dinner ThinkTank*

SC5: PD-L1 Assays for Biomarkers and Companion Diagnostics

*Separate registration required

Wednesday, May 3

7:30 am Morning Coffee

 

Immune Monitoring: Biomarkers of Response to Immunotherapy

 7:55 Chairperson’s Remarks

Michael J. Overman, M.D., Associate Professor, Gastrointestinal and Medical Oncology, The University of Texas MD Anderson Cancer Center

8:00 Immune-Profiling Platform 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.

Personal Genome Diagnostics 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 development in the PD-1 field have shown promising progress in combination of checkpoint inhibitors and cancer vaccines. However, one critical point hasn’t been answered yet, what is probably the initial pitfall of cancer vaccines, is the question how an effective immune response should look like and how this immune response can be monitored.

9:45 Coffee Break in the Exhibit Hall with Poster Viewing

 

New Directions in Personalized Cell Therapy and Combinations

 

10:45 CAR T Cells for Hematologic Malignancies

David L. Porter, M.D., Director, Blood and Marrow Transplantation; Jodi Fisher Horowitz Professor, Leukemia Care Excellence, University of Pennsylvania

Chimeric antigen receptors (CARs) combine an antigen recognition domain of an antibody with intracellular T cell signaling domains. Gene transfer techniques introduce the CAR into normal T cells redirecting them to target new antigens. CAR T cells targeting CD19 have unprecedented activity in relapsed and refractory B cell neoplasms including ALL, CLL and NHL. Newer approaches are being developed to enhance the activity, application, and safety of CAR T cells.

11:10 Tumor Microenvironment Modulation by Focal Adhesion Kinase Inhibitors

David Weaver, Ph.D., Vice President, Translational Medicine, Verastem

An immunosuppressive tumor microenvironment develops in many cancers. Immunotherapies can be more effective by combining with agents that modulate the tumor microenvironment. FAK inhibitors in Phase I and Phase II clinical trials and the preclinical rationale supporting these agents and their use in combination therapies will be introduced. The essential role of biomarkers of response and patient stratification will be discussed. 

11:35 Close of Conference