Cambridge Healthtech Institute’s Second Annual

Combination Immunotherapy

June 11-12, 2018 | Westin Boston Waterfront | Boston, MA



The future of immuno-oncology drug development is positioned in combination therapies, where immunotherapy modalities are tested in rational combinations with other immunotherapies or targeted therapies for synergistic effects. Combination immunotherapy promises to deliver long-term survival benefits that may be unavailable with current approaches. The Second Annual Combination Immunotherapy meeting will explore the most effective combinations of immunotherapy with conventional cancer therapy, with other immunotherapy or with targeted therapy. Coverage will include understanding the mechanism of action, managing toxicity, strategies to design synergistic combinations, biomarker development and case studies of ongoing combination immunotherapy studies from the leading researchers in industry and academia.

Final Agenda

Sunday, June 10

4:30-6:30 pm Short Course and Conference Registration

5:00-8:30 Dinner Short Course*

SC1: Fit-for-Purpose Biomarker Assay Development and Validation

*Separate registration required

Monday, June 11

7:00 am Conference Registration and Morning Coffee

8:00 Organizer’s Welcome

 

OPENING PLENARY SESSION: EMERGING APPROACHES FOR CANCER

8:05 Chairperson’s Opening Remarks

George A. Green, IV, PhD, Head, Pharmacodiagnostics, Bristol-Myers Squibb

8:10 Clinical Genomic Profiling Using the MSK-IMPACT™ Large Panel NGS Assay to Guide Patient Selection for Targeted and Immune Therapies

Marc Ladanyi, MD, William J. Ruane Chair in Molecular Oncology, Molecular Diagnostics Service and Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center

As the centerpiece of an institutional initiative in clinical cancer genomics, we have implemented large scale genomic profiling for targetable cancer drivers and other cancer-relevant alterations in all patients with advanced solid cancers. Since 2014, over 23,000 patients have been profiled using the MSK-IMPACT™ targeted large panel, capture-based DNAseq assay. MSK-IMPACT™, which received FDA clearance in 2017, allows robust detection of somatic mutations in all known cancer genes, copy number changes and select cancer fusion gene rearrangements, as well as assessing overall tumor mutation burden and microsatellite instability. Patients are also screened for oncogenic fusions by targeted RNAseq and for germline cancer predisposition alleles and evidence of clonal hematopoiesis.

8:40 Widgets to Cancer Patient-Specific Digits: The Case for Out-of-Clinic Objective Measures and Their Potential Impact to Remote Patient Monitoring in Precision Oncology and Discovery

Christopher M. Hartshorn, PhD, Program Director, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health

Albeit the case for long-term, out-of-clinic monitoring has been obvious for many chronic diseases, the case for cancer has not been as clear. The National Cancer Institute has begun piloting and funding various aspects to enable an Internet of Cancer Medical Things. This talk will focus on these efforts currently and prospectively as well as the overall vision to coordinate a much broader initiative to improve our understanding of cancer progression and improve the delivery of cancer care.

9:10 Coffee Break in the Exhibit Hall with Poster Viewing

 

BIOMARKERS FOR COMBINATION IMMUNOTHERAPY

9:55 Chairperson’s Remarks

Carol Anne Ogden, PhD, Senior Manager and ADCETRIS Biomarker Lead, Diagnostics and Biomarkers, Seattle Genetics, Inc.

10:00 Looking under the Spotlight: Evaluation of Biomarkers in an ADC + CPI Combination Clinical Trial

Carol Anne Ogden, PhD, Senior Manager and ADCETRIS Biomarker Lead, Diagnostics and Biomarkers, Seattle Genetics, Inc.

Brentuximab vedotin (BV) is an antibody-drug conjugate directed against CD30, a receptor expressed by malignant Reed-Sternberg (RS) cells present in classical Hodgkin lymphoma. Treatment with BV may result in inflammatory activity due to RS destruction by immunogenic cell death. Nivolumab blocks the programmed death-1 (PD-1) receptor, inhibiting the binding of PD-1 ligands, and together with the inflammatory activation activity of BV, restores the antitumor immune response.

10:30 Prognostic and Predictive Markers for Immunotherapy and Combination Therapy

Kathleen M. Mahoney, MD, PhD, Clinical Instructor, Beth Israel Deaconess Medical Center; Research Fellow, Dana-Farber Cancer Institute

11:00 Forward and Reverse Strategies to Support the Clinical Development of the Anti-PD-1 Antibody Pembrolizumab

Sarah Javaid, PhD, Associate Principal Scientist, Merck

Immune checkpoint blockade therapies are revolutionizing the standard cancer treatment. Despite the current success of these therapies, not all patients respond to immunotherapy and even those that do often experience toxicities. Combination approaches are the keys to improving clinical response. Novel high throughput technologies enable us to understand the mechanisms underlying the complex interactions between the immune system and cancer, identify predictive biomarkers for the patients who will most likely benefit from current immunotherapies, avoid immune-related adverse events and reduce treatment costs for those unlikely to respond.

Signals Analytics11:30 From a Test Tube to a Business Opportunity - The Power of an Intelligence Platform

Shlomi Madar, Vice President, Life Sciences, Signals Analytics

Soon, the doubling time of medical knowledge will reach 75 days! This new reality requires a whole new mindset. Connected Intelligence is a new concept that allows the decision maker to assume control over big data and convert it into meaningful, actionable insights. Learn more @ Signals Analytics' talk.

12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

 

RATIONAL COMBINATION IMMUNOTHERAPY STRATEGIES

1:25 Chairperson’s Remarks

Emmett Schmidt, MD, PhD, Scientific Associate Vice President, Merck Research Labs

1:30 Drivers in the Clinical Development of Cancer Combination Therapy

Emmett Schmidt, MD, PhD, Scientific Associate Vice President, Merck Research Labs

Immune checkpoint inhibition is emerging as a backbone for cancer therapy. Data from a broad range of combination trials containing such therapies have emerged in the last three years. Combination benefit by independent action and through molecular reasoning both fit portions of these developing results. A flexible application of both approaches to future trial development seems likely to yield rewards in combination therapy development.

2:00 Shifting Perspectives on Combination Immunotherapy

Maria Karasarides, PhD, Executive Director, Immuno-Oncology, Regeneron Pharmaceuticals

This presentation will cover: 1) emerging immunotherapy combination data and meaningfulness of early data sets, 2) focus on PD-1 and CTLA-4 blockade – is this the most promising combination to date? 3) strategies to improve immunotherapy combinations development – is patient selection our best bet?

2:30 Dual Checkpoint Inhibition DART® Molecules

Edwin Rock, MD, PhD, Vice President, Clinical Research, MacroGenics, Inc.

Combinations of multiple checkpoint inhibitors have resulted in significantly enhanced benefit compared to the blockade of a single target. DART molecules are designed to simultaneously bind to two targets. MGD013 (co-blockade of PD-1 and LAG-3) and MGD019 (co-blockade of PD-1 and CTLA-4), are DART molecules that could deliver biological and clinical activity of combined checkpoint blockade using a single molecule with potential advantages in biology, clinical development and patient convenience.

3:00 The Impact of Patient-to-Patient Variability on Responses to Combination Therapies

Adam C. Palmer, PhD, Postdoctoral Fellow, Harvard Program in Therapeutic Science, Harvard Medical School

All cancer therapies have variable efficacy across patient populations. With combination therapies, different patients may be more or less responsive to different parts of the combination. This has two consequences that affect the design and interpretation of clinical trials. First, patient variability alone, without 'drug additivity,' explains the superiority of many FDA-approved combinations including PD1 + CTLA4 blockade. Second, when trials compare 'treatment A' vs 'A + B', improved survival curves can be equally explained by (1) most patients experiencing a small benefit or (2) few patients experiencing a large benefit: this imposes massive uncertainty on estimates of the rate and magnitude of survival benefit from adding treatment 'B'.

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

 

PERSONALIZED VACCINES: POTENTIAL FOR COMBINATION IMMUNOTHERAPY

4:10 Chairperson’s Remarks

Emmett Schmidt, PhD, Distinguished Scientist & Executive Director, Merck Research Labs

4:15 Cancer Vaccines: Advances, Challenges and Opportunities

Marijo Bilusic, MD, PhD, Associate Research Physician, National Cancer Institute, National Institutes of Health

Therapeutic cancer vaccines are unlikely to impact treatment outcomes as monotherapy. There is growing preclinical and clinical data that combination with other treatment modalities like chemotherapy, hormone therapy or immunotherapy can enhance treatment efficacy and induce immunogenic intensification with minimal additional toxicity. It seems that therapeutic vaccines with checkpoint inhibitors holds the greatest potential for improving clinical outcomes.

4:45 The Next Wave: Combination Immunotherapy with Vaccines Targeting a New Class of Cancer Antigens, Combined with T Cell Agonists and Checkpoint Blockers

Bernard A. Fox, PhD, Harder Family Chair for Cancer Research, Member and Chief, Laboratory of Molecular and Tumor Immunology, Robert W. Franz Cancer Center, Earle A. Chiles Research Institute, Providence Portland Medical Center; CEO, UbiVac

Using a microvesicle vaccine composed of SLiPs and DRiPs, and termed DRibbles (DRiPs in Belbs), in a tumor model that lacks apparent immunogenicity, and where anti PD-L1 has no effect, we find that DRibble vaccination combined with anti-OX40 can substantially boost therapeutic efficacy and result in apparent cure of animals. We have performed a Phase II trial of this strategy as adjuvant treatment for definitively treated NSCLC and document induction or boosting of immune response to a wide spectrum of proteins whose genes are overexpressed in NSCLC.

5:15 Dissecting Immune Correlates in Cancer Immunotherapy Clinical Trials

Steven Fling, PhD, Senior Staff Scientist, Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center; Director, Cancer Immunotherapy Trials Network Immune Monitoring Laboratory

Our lab coordinates multi-parameter, immune monitoring of multi-center cancer immunotherapy trials. We recently reported clinical results from a vaccine therapy trial in cancer patients with advanced malignancies expressing NY-ESO-1, showing significantly increased humoral and cellular immunity resulting from the vaccine regimen. Here we report techniques and in-depth results dissecting multiple correlates associated with the enhanced immune response to vaccine, including gene signatures and delineation of antigen presenting cell subsets.

5:45 Welcome Reception in the Exhibit Hall with Poster Viewing

Tuesday, June 12

7:25 am Interactive Breakout Discussion Groups with Continental Breakfast

 

TARGETING THE TUMOR MICROENVIRONMENT: ACTIVATING THE IMMUNE SYSTEM FOR BETTER RESPONSE TO IMMUNOTHERAPY

8:25 Chairperson’s Remarks

John Milburn Jessup, MD, George Mason University

8:30 Immunogenic Cell Death: An Agnostic Adjuvant for Mice and Men

John Milburn Jessup, MD, Scientific Director, Precision Cancer Care Program, Inova Schar Cancer Institute; Professor, Systems Biology, Krasnow Institute of Advanced Study, George Mason University

Immunogenic cell death is a form of necroptosis caused by viruses, select cytotoxic agents and radiation that causes the release of tumor antigens in association with eat me and take me signals that promote innate immunity as well as cross-prime adaptive immune responses to the tumor. The advantage of this approach is that it is agnostic to the specific tumor antigen and stimulates the host to determine what may be important as an immune response. Our approach in human and mouse colorectal carcinoma involves combining a viral therapeutic with a standard cytotoxic agent to induce cell-mediated immunity to tumor antigens that then may be augmented by checkpoint inhibitors.

9:00 Modulating Intratumoral Myeloid Cells to Prime Responses to Anti-PD-1 Blockade

Robert Pierce, MD, Scientific Director, Immunopathology Core, Fred Hutchinson Cancer Research Center

Anti PD-1 blockade is effective in many solid tumors, but response appears to be predicated on a preexisting anti-tumor T cell response. Immunologically quiescent tumors generally fail to respond. The tumor microenvironment (TME) of these poorly inflamed tumors are often dominated by myeloid-derived (MF) immunosuppressive cells. Using experimental mouse models and human tumor samples, we describe various immunosuppressive states of intratumoral MF and potential means to reverse the immunosuppressive TME through modulating these cells.

9:30 Activated B Cells in Human Primary Tumors Present Antigen and Increase Anti-Tumor Function of CD4 T Cells

Tullia Bruno, PhD, Research Assistant Professor, Immunology, University of Pittsburgh

immunoSCAPE10:00 Mass Cytometry Approaches to Biomarker Discovery via High-Dimensional Antigen-Specific T Cell Identification and Profiling

Ghislain Bonamy, PhD, Associate Director, Business Development, immunoSCAPE

immunoSCAPE leverages the high-dimensional immune profiling capabilities of mass cytometry combined with a unique technology to identify and profile antigen-specific T-cells, including T-cells recognizing tumor-derived neoantigens. We will show examples of how simultaneous in-depth T-cell characterization enables discovery of biomarkers of clinical response and assessment of immunotherapy biological activity.

 

10:30 Coffee Break in the Exhibit Hall with Poster Viewing

 

TUMOR NEOANTIGENS AS BIOMARKERS AND TARGETS

11:10 Chairperson’s Remarks

Fred Ramsdell, PhD, Parker Institute for Cancer Immunotherapy

11:15 Neoantigens and Their Relationship to Mutational Load, Mismatch Repair and Immune Checkpoint Expression

Arnold B. Gelb, MD, MS, FASCP, FCAP, Clinical Advisor, Exploratory Biomarkers

The objectives of this presentation are: 1) to review the biological background by which somatic mutations can lead to the generation of private, highly immunogenic tumor antigens (neoantigens), 2) to discuss association of neoantigens with mutational burden, mismatch repair and immune checkpoint expression, and 3) to provide an outlook on clinical applications involving assessment of neoantigens and mutational load with regards to response to immune-checkpoint blockade in solid tumors.

11:45 Tumor Neoantigen Selection Alliance (TESLA): Towards Personalized Cancer Vaccines

Fred Ramsdell, PhD, Vice President, Research, Parker Institute for Cancer Immunotherapy

It is now accepted that mutation-derived neoantigens can elicit a tumor-specific immune response. Identifying neoantigens accurately from the exome sequence is a key parameter for the development of such responses and remains a significant variable of the overall process. TESLA is a consortium-based approach involving over 30 groups to identify key parameters in neoantigen prediction. An update on the progress of the program will be discussed.

12:15 pm Driving CD8+ T Cell Responses to Mutational Neoantigens in Tumors—Harnessing Immunogenic Viral Vectors in Combination with Immune Checkpoint Modulators

Karin Jooss, PhD, CSO, Gritstone Oncology

DNA damage may cause mutations in tumors that can generate new antigens, known as tumor-specific neo-antigens (TSNAs). Accurate prediction of TSNAs is key to generate potent TSNA specific vaccine approaches. Viral vector-based vaccine platforms have shown to induce hi-titer, polyfunctional and durable CD4+ and CD8+ T cell responses in humans. The personalized vaccine is delivered in combination with immune checkpoint blockade, to keep TSNA-induced T cells active in the immunosuppressive tumor microenvironment.

12:45 Session Break

almac12:55 Luncheon 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.

1:25 Close of Conference