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Cambridge Healthtech Institute’s Inaugural
Combination Cancer Immunotherapy
Strategies for Increasing the Efficacy of Cancer Immunotherapy by Combining Emerging Antibody Therapeutics with Classic and Novel Biotherapeutics
August 12-13, 2014


Overview/Description: Speaker Biographies 

It is now established that most immune modulating antibody-based immunotherapies offer more benefit to the patient by being administered in combination with other traditional forms of cancer management or in tandem with other checkpoint inhibitors and/or co-stimulatory agonists. A wave of clinical trials is now underway to explore new combinations and how they should be dosed and sequenced for maximum efficacy.

Combination Cancer Immunotherapy seeks to advance this field by offering researchers and clinicians a forum in which to examine the treatment strategies that will be most effective as this field evolves. Presentations will explore how individual components are identified and developed for use in combinations, how to design combinations for maximum effect in specific tumor types and the conclusions that can be drawn from recent trials of common combination types. The meeting also will examine the best ways to combine new understandings of immunotherapy with new advances in biotherapeutic product formats – and then how to advance these programs through regulatory approval and into clinical application.


Recommended Dinner Short Course*

Cancer Vaccines: Clinical Updates, New Technologies and Challenges 


*Separate registration is required.


TUESDAY, AUGUST 12

12:30 Conference Registration

1:55 pm Chairperson’s Opening Remarks

Peter P. Lee, M.D., Billy and Audrey L. Wilder Endowed Professor, Chair, Department of Cancer Immunotherapeutics & Tumor Immunology, City of Hope Comprehensive Cancer Center

2:00 Keynote Presentation:

Update from 2014 ASCO Meeting: Clinical Trials for Immunotherapy Combinations

Omid HamidOmid Hamid, M.D., Director, Melanoma Center, Angeles Clinic and Research Institute

After significant success in the field of Immuno-Oncology in multiple solid tumors, focus has shifted to combinations of immunotherapies. A combinatorial approach with each other or with other therapeutic modalities could potentially lead to enhanced efficacy, improved response rate, progression-free survival and overall survival. Despite this enthusiasm, initial trials have been frought with toxicity. This presentation will focus on recent data on state-of-the-art combinations with discussion on efficacy, outcome, dosing and applicability across many tumor types.


ADVANCES IN CANCER IMMUNOLOGY THAT IMPACT COMBINATION THERAPY

2:45 Restoring and Enhancing Host Immune Function in Cancer

Peter P. LeePeter P. Lee, M.D., Billy and Audrey L. Wilder Endowed Professor, Chair, Department of Cancer Immunotherapeutics & Tumor Immunology, City of Hope Comprehensive Cancer Center

Host anti-tumor immune responses play an important role in achieving durable clinical responses even with chemotherapy, leading to the novel concept of immunogenic cell death. Successful treatment of patients with advanced metastatic disease will be crucially dependent on synergistic drug combinations able to effectively modulate immunogenic cell death and restore/enhance anti-tumor immune responses. We will report on our recent results in identifying synergistic drug combinations that can induce immunogenic cell death and restore/enhance immune function.

3:15 Sponsored Presentation (Opportunity Available)

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

4:15 Defining T Cell Pathways Engaged by Combination Checkpoint Blockade Immunotherapy

Ryan TeagueRyan Teague, Ph.D., Assistant Professor, Molecular Microbiology & Immunology, Saint Louis University School of Medicine

Blockade of T cell inhibitory signaling pathways is being pursued for immunotherapy in cancer patients, but the biochemical pathways being targeted in responding T cells are not well characterized, particularly for combination treatments. To achieve the promise of immunotherapy it is vital to define molecules key to a clinically successful response. Our work strives to define the operative T cell mechanisms elicited during checkpoint blockade, providing translational insight for the treatment of patients with cancer.

4:45 Immune Corrective Strategies

Samir Khleif, M.D., Director, GRU Cancer Center; Professor of Medicine, Medical College of Georgia

 


SPECIAL PRESENTATION

5:15 Lifting the Curve & Raising the Bar: The Impact of Immunotherapy on the Cancer Therapeutics Market

Seamus FernandezSeamus Fernandez, Managing Director, Leerink Partners

Curing cancer has been an elusive goal. Today, with ipilimumab and PD1/PDL1 antibodies “lifting the curve” and data suggesting combinations will achieve even broader and deeper responses, the market must prepare for this goal to become a reality. Given the economic cost of drug development and expected pressures on payer reimbursement it is critical to understand the role of a backbone therapy, the importance of biomarker-based patient selection, and the implications of a raised bar for existing and future cancer therapy.

5:45 End of Day


WEDNESDAY, AUGUST 13

7:45 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

8:25 Chairperson’s Opening Remarks

Adam J. Adler, Ph.D., Associate Professor, Immunology, University of Connecticut


STRATEGIES FOR COMBINATION IMMUNOTHERAPY

8:30 Strategies for Combining Immunotherapy with Radiation Therapy

James W. WelshJames W. Welsh, M.D., Assistant Professor, Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center

The biological premise behind such a strategy is that the tumor antigen release achieved by localized radiation will promote specific adaptive immune system targeting, which can be augmented further by systemic immune-stimulating agents. Clinicians hope to induce a phenomenon known as the abscopal effect, where localized radiation results in immune-mediated tumor regression in disease sites well outside of the radiation field. I present a review of the early clinical and pre-clinical evidence behind this approach, with emphasis on treatment of non-small cell lung cancer.

9:00 Genomic Determinants of Sensitivity to Immunotherapeutics

Peter HammermanPeter Hammerman M.D., Ph.D. Assistant Professor of Medicine, Department of Molecular and Cellular Oncology, Harvard Medical School

Genomic discovery efforts performed across multiple tumor types have identified key molecular alterations involved in tumorigenesis. A surprising result from these studies is that many tumor types harbor somatic alterations in genes which have an impact on immunity. Here, I will describe somatic alterations in key immunomodulatory genes in cancer, genomic studies of tumors and the microenvironment which have suggested particular vulnerabilities to immunotherapies and the use of transgenic animals with intact immune systems and relevant mutational profiles to study immunotherapies pre-clinically.

9:30 Combination of Immune Therapies in Preclinical Models

Li-Fen Lee, Ph.D., Senior Principal Scientist, Rinat, Pfizer

From a drug development and clinical care perspective, the activity observed with anti-PD-1 is clear. Robust single agent activity was observed and for durable and persisted without off-target toxicity. However, as we learn from the clinical trial data to date, the majority of patients will not respond or will have incomplete response to anti-PD-1. Because other immune regulation mechanisms of immunosuppression that work together or in parallel with PD-1 we explore different combinations in different tumor syngeneic animal models. We focus on tumors that are resistant to single agent treatment. The detailed efficacy and mechanisms will be discussed.

10:00 Sponsored Presentation (Opportunity Available)

10:15 Coffee Break in the Exhibit Hall with Poster Viewing

11:00 Targeting Antigen-Loss Tumor Variants through CD134 Plus CD137 Agonist Combination Therapy

Adam J. AdlerAdam J. Adler, Ph.D., Associate Professor of Immunology, University of Connecticut

Costimulatory receptor agonists can elicit T cell-mediated anti-tumor immunity. Further, combining different agonists can enhance therapeutic efficacy. In particular, dual costimulation through CD134 (OX40) plus CD137 (4-1BB) engages multiple immune cells with tumoricidal potential that include cytotoxic CD8+ T cells and, surprisingly, cytotoxic CD4 Th1 cells. In addition to directly targeting tumors, dual-costimulated cytotoxic CD4 Th1 cells also orchestrate a bystanding helper response that can target antigen-loss tumor variants.

11:30 Prospects for Combination Immunotherapy for Hepatobiliary and Pancreatic Cancers

Neeharika Srivastava, M.D., Instructor in Medicine, Harvard Medical School; Faculty, Division of Hematology/Oncology, Beth Israel Deaconess Medical Center (BIDMC)

Hepatobiliary and pancreatic cancers are notoriously difficult to treat, largely due to high recurrence rates and resistance to traditional chemotherapies. Several clinical trials of immune therapy in these malignancies have demonstrated promising results, although none have produced a survival benefit. Combination immunotherapy may boost efficacy. Current avenues of research are discussed and potential opportunities are explored.

12:00 pm Immune Modulation and Combined Immunotherapies Using Gold Nanoparticles

Aaron FosterAaron Foster, Ph.D., Director, Product Discovery, Bellicum Pharmaceuticals

Gold represents a flexible and inert material to design nanoshells for thermal ablation of tumors, or to functionalize with molecules to modulate immunity for use as a single cancer therapy or in combination with other immunotherapies such as adoptive T cell transfer and vaccines. Our work examines how to use gold nanoparticles as an adjuvant to stimulate tumor-specific T cell responses and to disrupt immune suppressor cells to enhance immunotherapy.

 

12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own


CLINICAL UPDATES OF COMBINATION IMMUNOTHERAPIES

1:55 Chairperson’s Remarks

Marc Mansour, Ph.D., COO, ImmunoVaccine

2:00 Key Issues in the Clinical Development of Immunotherapy Combinations

Jason J. LukeJason J. Luke, M.D., Melanoma Disease Center, Dana-Farber Cancer Institute; Instructor, Harvard Medical School

Immunotherapy is on the verge of relevancy in many cancers and combinations with other modalities (immuno-, chemo/targeted therapies and radiation) are imminent. Beyond a strong preclinical rationale for combinations, careful selection of endpoints in clinical trials will be important. Historically, response rate and progression-free survival were considered useful surrogate endpoints however immunotherapy may not fit this model. Further, the toxicities of combinations will need to be considered closely within different cancers and patient populations.

 

2:30 Presentation Title to be Announced 

Taha Merghoub, Ph.D., Associate Biologist, Memorial Sloan-Kettering Cancer Center

 

3:00 Combined Treatment Using Adoptive Cell Therapy, IL-2, and Tumor-Specific Antibodies

Cary F. OpelCary F. Opel, Researcher, Wittrup Lab, Chemical Engineering, Massachusetts Institute of Technology

IL-2 is frequently given alongside other immunotherapies to enhance immune response. The protein, however, has poor pharmacokinetic properties and negative side effects. Our pre-clinical work combines a persistent form of IL-2 with adoptive cell transfer and a tumor-targeting antibody, resulting in tumor regression and, in some cases, complete cures with immunological memory. These results show adjuvants such as extended pharmacokinetic IL-2 can potentially improve the clinical outcomes of other targeted immunotherapies.

3:30 Refreshment Break

3:45 What Can We Expect Immunologically and Clinically from Combining an Immune Modulator with the Survivin Targeting Vaccine DPX-Survivac?

Marc MansourMarc Mansour, Ph.D., COO, ImmunoVaccine

DPX-Survivac is a depot based cancer vaccine designed to generate robust CD8 T cells against survivin, a therapeutic target associated with solid tumors and blood cancers. Combining DPX-Survivac with metronomic cyclophosphamide has demonstrated significantly increased its immunogenicity in advanced cancer patients. We have additional data to suggest that combination therapy diminishes the immune suppression at the tumor level to enhance the activity of the treatment. Grouping of this therapy with checkpoint inhibitors can further drive tumor specific immune responses.

4:15 Combinations with CRS-207, a Live-Attenuated Listeria Monocytogenes Expressing Mesothelin

Dirk BrockstedtDirk Brockstedt, Ph.D.,Senior Vice President, Research & Development, Aduro Biotech, Inc.

Aduro BioTech recently completed a Phase 2 trial of the combination of CRS-207 and GVAX Pancreas immunotherapies in patients with advanced-stage metastatic pancreatic cancer. This is the first randomized study to show that immunotherapy is effective in pancreatic cancer, and Aduro has initiated the follow-on Phase 2b ECLIPSE trial. Aduro is also conducting an ongoing Phase 1 trial of CRS-207 in combination with chemotherapy in patients with malignant pleural mesothelioma.

4:45 Applications of Systems Biology for Characterizing Mechanism of Action and Biomarker Discovery in Cancer

Craig Meagher, Ph.D., Senior Scientist, Research, Dendreon Corporation

Better characterization of the immunological mechanism of action against tumors and the identification of predictive and pharmacodynamic biomarkers of clinical outcome are important needs for cancer immunotherapies. We are using various high-content platforms to address such needs for sipuleucel-T, an autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic, metastatic castration-resistant prostate cancer. Results from some of these investigations will be presented. Such approaches may be broadly applicable for other cancer immunotherapies and may assist in assessing immunotherapy combinations in cancer.

5:15 Close of Conference