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Cambridge Healthtech Institute’s 5th Annual

Rational Combination Cancer Immunotherapy

A Forward-Looking View of the Science and Strategies that Will Inform the Discovery and Development of Effective Immunotherapy Combinations
August 29-30, 2017 | Sheraton Boston Hotel | Boston, MA


The clinical and regulatory successes of checkpoint proteins are driving a resurgence of interest in immunotherapy as a primary form of cancer treatment, with numerous clinical studies exploring the application of these therapeutics in combinations with traditional and experimental agents. CHI’s 5th Annual Rational Combination Cancer Immunotherapy takes a forward-looking perspective on the design of drug products and treatment progressions that will build on the knowledge arising from these exploratory trials. The meeting will explore the scientific and strategic considerations for different immunotherapy combination strategies – and consider the business and clinical challenges facing research organizations wanting to successfully link their therapeutic programs to approved checkpoint inhibitors.



Final Agenda

TUESDAY, AUGUST 29

12:00 pm Registration

1:15 Chairperson’s Opening Remarks

Elena Spanjaard, Ph.D., Director, Worldwide Research & Development, Regulatory Affairs, Pfizer


1:20 Keynote Presentation: Combination Cancer Immunotherapy: Current State and Future Opportunities

Jon Wigginton, M.D., CMO, Senior Vice President, Clinical Development, MacroGenics

This presentation considers the guiding principles in the clinical development of immune-oncology combinations, to include patient selection, dose and schedule selection and optimizing risk/benefit. I will also discuss future opportunities for the clinical development of immuno-oncology combinations and provide analysis of the unique role and key considerations for bispecific approaches for combination immunotherapy.

CLINICAL EVALUATION OF IMMUNOTHERAPY COMBINATIONS

1:50 Regulatory Perspectives on Early Clinical Development in a Combinatorial World

Elena_SpanjaardElena Spanjaard, Ph.D., Director, Worldwide Research & Development, Regulatory Affairs, Pfizer

Efficient co-development of novel combination therapies presents complex regulatory challenges that require modality-specific approaches. Current regulatory guidelines provide a framework for early development of investigational agents that are intended for use in combination. Regulatory concepts that address preclinical and clinical development of immuno-oncology combinations will be reviewed, and key considerations will be highlighted for various treatment modalities.

2:20 Application of Patient-Derived Xenografts in Immuno-Oncology Pre-Clinical Discovery, Target Validation, and Clinical Trials

Ryan_SowellRyan T. Sowell, Ph.D., Postdoctoral Fellow, Immunobiology, Yale University School of Medicine

Immuno-oncology faces major challenges in expediting the path of discovery to the clinic. As the number of targets grow, so does a need to rapidly validate them and the nearly infinite potential combinations therof. We will discuss how emerging humanized mouse models and single cell analyses can aid the rational design of combination therapies, while also providing opportunities to gain deep insight into biology that drives patient responses to immunotherapy.

2:50Featured Poster Presentation: Inhibition of MMP9 Yields Improved Effector T cell Responses in a PD1-Axis Refractory Model

Chris_OSullivanChristopher L. O’Sullivan, Associate Scientist, Biologics and Target Biology, Gilead Sciences

We developed a monoclonal antibody that inhibits murine MMP9 and assessed its mechanism of action in immunocompetent mice alone or in combination with a murine anti-PDL1 antibody. A model of Her2-driven breast cancer was utilized for both efficacy and pharmacodynamic studies involving RNA and T cell receptor sequencing, enzymatic analyses, and flow cytometry. Inhibition of MMP9 reduced tumor burden and promoted cytotoxic T cell infiltration in this PD1-axis refractory model.

3:20 Refreshment Break in the Exhibit Hall with Poster Viewing


4:00 PLENARY KEYNOTE SESSION

4:00 Regulatory and Scientific Considerations for Cancer Vaccines and Adoptive Cellular Immunotherapy

Graeme E. Price, Ph.D., Research Microbiologist, Gene Transfer & Immunogenicity, FDA CBER

Cell and Gene therapy including therapeutic vaccines and cellular immunotherapy products are evaluated at FDA’s Center for Biologics Evaluation and Research in the Office of Tissues and Advanced Therapies (OTAT) previously known as Office of Cellular, Tissue and Gene Therapies. I will discuss current general regulatory and scientific considerations in the regulation of therapeutic cancer vaccines and cellular immunotherapy. In addition, research activities in OTAT will be summarized.

4:45 Market Access and Reimbursement for Immuno-Oncology Drugs in Today’s Healthcare System

Gergana Zlateva, Ph.D., Vice President, Payer Insights and Access, Oncology, Pfizer

Now that immunotherapies have hit the market, with the promise of more to come, the healthcare system will need to establish standards for cost and reimbursement of immuno-oncology agents. This talk will address how the healthcare marketplace can prepare for the adoption of novel pricing and reimbursement models to increase patient access to immunotherapies. Establishing the value of IO therapies to payers and HTAs will also be addressed in the context of pricing and evidence generation.

Click here for keynote biographies

5:30 Welcome Reception in the Exhibit Hall with Poster Viewing

5:30 Dinner Short Course Registration*

SC1: Bioinformatics for Immuno-Oncology and Translational Research

SC2: Microbiome in Immuno-Oncology

*Separate registration required, please click here for more information.

WEDNESDAY, AUGUST 30

7:00 am Registration

7:25 Breakout Discussion Groups with Continental Breakfast

Join a breakout discussion group. These are informal, moderated discussions with brainstorming and interactive problem solving, allowing participants from diverse backgrounds to exchange ideas and experiences and develop future collaborations around a focused topic. Details on the topics and moderators are below.

Clinical Trial Design for IO Combinations

Moderator: Osama E. Rahma, M.D., Assistant Professor, Medicine, Center For Immuno-Oncology, Gastrointestinal Cancer Center, Dana-Farber Cancer Institute

  • Biomarkers and clinical endpoints
  • Incorporating prior PD-1 resistance
  • Maximizing the value of phase 1 trials
  • Novel trial designs, adaptive trials
  • Regulatory considerations in combination trials

Combination Therapies and the Tumor Microenvironment

Moderator: Allison S. Betof, M.D., Ph.D., Medical Oncology Fellow, Memorial Sloan Kettering Cancer Center

  • What are recent combination trials telling us about the MOA of combinations in the microenvironment?
  • The role of metabolism in immunobiology , and how this impacts the design of immunotherapy combinations
  • Strategies for immune system priming and activation
  • Control of immune-related adverse events
  • Biomarkers and patient stratification

 

IMMUNOTHERAPY COMBINATION STRATEGIES

8:25 Chairperson’s Remarks

Art Krieg, M.D., Founder, President and CEO, Checkmate Pharmaceuticals

8:30 Four-Ingredient Antibody Cocktail for Cancer Immunotherapy

Dane_WittrupK. Dane Wittrup, Ph.D., Carbon P. Dubbs Professor, Chemical Engineering and Biological Engineering, Massachusetts Institute of Technology

We have determined that the combination of an anti-tumor antibody (A), IL-2 (I), anti-PD-1 antibody (P), and a therapeutic vaccine (V) is a highly efficacious and well-tolerated immunotherapy against established syngeneic tumors in mice. The AIPV formalism can be extended to include other agents; we have explored the use of an integrin-targeted Fc fusion that may also provide some degree of the I and V components of an AIPV therapy.

9:00 ADC Strategies for Cancer Immunotherapy

Ryan HeiserRyan Heiser, Ph.D., Senior Scientist, Immunology, Seattle Genetics

ADCs have shown favorable results in numerous clinical trials, improving the tolerability of potent, broadly acting cytotoxins. The same properties that make ADCs attractive as single agents also enable them to be preferred partners for combinations with immunotherapy. This talk will provide an overview of the preclinical and clinical results of these combinations.

9:30 Combination Therapy with Anti-PD-1 and CMP-001, A CpG-A Oligodeoxynucleotide in a Virus-Like Particle, Can Induce Tumor Regression in PD-1 Refractory Patients with Advanced Melanoma

Art_KriegArt Krieg, M.D., Founder, President and CEO, Checkmate Pharmaceuticals

Anti-PD-1 therapy can induce regression of tumors that are immunologically “hot”, but has generally been ineffective in treating tumors that are immunologically “cold”. We have now demonstrated that activation of tumor-infiltrating plasmacytoid DC (TI-pDC) through TLR9 by CMP-001 converts “cold” tumors to create a “hot” IFN-rich tumor microenvironment and, in combination with systemic anti-PD-12 therapy, induces local tumor regression and abscopal regression of visceral metastases in patients with PD-1 refractory advanced melanoma.

10:00 Featured Poster Presentation: Immune Checkpoint Inhibitors for the Treatment of Human Colon Carcinoma in the hPBMC-NCG Humanized Mouse Model

Paula Miliani de Marval, Ph.D., Research Associate Director, Charles River Laboratories Discovery Services

The availability of NSG, NCG and NOG superimmune-deficient mice have proven instrumental in the development of humanized mouse models.  These models offer unique tools to assess the anti-tumor response to immune-checkpoint inhibitors in animals bearing a human immune environment.  The work presented here shows that NCG mice successfully engraft with hPBMC providing a suitable model for pre-clinical immune-oncology studies.  The results from these studies will be discussed in this presentation.

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

11:15 Risk Assessment Strategies for Immunotherapy Combinations: Should My PD-1/PD-L1 Backbone Come from a Partner or via Internal Development?

Llew_KeltnerLlew Keltner, M.D., Ph.D., CEO, EPISTAT

Various counts of anti-PD-1/PD-L1 unique compounds in development range from several dozen to over 200. Such proliferation of development efforts to a single target is unprecedented in pharma. Clinical and financial realities demand that almost any IO modality be tested clinically with modulators of PD-1/PD-L1. Development, clinical trial, IP, regulatory and marketing issues related to the internal/external access decision will be summarized, with the expectation of open challenge and discussion.

11:45 Customizing Cancer Immunotherapies to Match the Intrinsic Tumor Microenvironment

Brad_NelsonBrad Nelson, Ph.D., Co-Director, Immunotherapy Program, British Columbia Cancer Agency, Canada

Focusing on gyneocological cancers, we apply 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 find that optimal anti-tumor immunity requires both T cells and antibody-producing B-lineage cells. We have identified three immune response patterns with distinct implications for immunotherapy. These insights are being translated to clinical trials of adoptive T cell therapy.

12:15 pm Preclinical and Clinical Update: Immunotherapy Combination of Monoclonal Antibodies Fused to Immune Effector Molecules

Sanjay Khare, Ph.D., President, ImmunGene

ImmunGene is developing a novel class of biotherapeutics called Focused-Interferon therapy or FIT to activate anti-tumor response in the tumor microenvironment (TME). This approach empowers antibodies by genetically fusing them to tumor cell-killing cytokines that can also activate host immune system locally in the TME. This presentation details preclinical and clinical updates of FIT technology.

Mitra Biotech12:45 Luncheon Presentation: Prioritizing Combinations Using a Human Phenotypic Model for Drug Development

Mark_ParisMark Paris, Ph.D., Associate Director, Translational Applications, Mitra Biotech


1:15 Session Break

BIOMARKERS AND TREATMENT PROGRESSION FOR IMMUNOTHERAPY COMBINATIONS

1:55 Chairperson’s Remarks

Ravi Madan, M.D., Clinical Director, Genitourinary Malignancies Branch, National Cancer Institute

2:00Combination Strategies to Overcome Resistance to Anti-PD-1/PD-L1 Therapies

Osama_RahmaOsama E. Rahma, M.D., Assistant Professor, Medicine, Center For Immuno-Oncology, Gastrointestinal Cancer Center, Dana-Farber Cancer Institute

Despite the encouraging response rate of variety of malignancies to anti-PD-1 and PD-L1 antibodies resistance do occur in most patients. Understanding the mechanism of resistance to anti-PD-1 and PD-L1 blockade remains challenging. We will explore hypotheses for this resistance and potential combinations that may overcome such resistance.

2:30 Rationale and Opportunities for Immunotherapy in the (Neo)Adjuvant Setting

Ravi_MadanRavi Madan, M.D., Clinical Director, Genitourinary Malignancies Branch, National Cancer Institute

Immunotherapy has rapidly been developed as a metastatic treatment for several cancers, but its greatest potential may be as part of (neo)adjuvant strategies in patients with localized and curable disease. Immunotherapy strategies in (neo)adjuvant prostate cancer will be discussed as a means to provide a template for similar studies in other cancers. Immune responses and imaging correlates will be discussed as possible biomarkers in such studies.

3:00 Emerging Immunotherapy Combinations in Non-Small Cell Lung Cancer

Justin_GainorJustin F. Gainor, M.D., Instructor in Medicine, Massachusetts General Hospital

Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis are now standard therapies in non-small cell lung cancer (NSCLC). Despite the impact of these agents, however, only a minority of patients respond to therapy. To enhance the activity of PD-1/PD-L1 inhibitors in NSCLC, efforts are ongoing to develop rationale combination approaches. This presentation will describe emerging PD-1/PD-L1 inhibitor combination strategies in NSCLC, including chemotherapy, vaccines, targeted therapies, co-inhibitory and co-stimulatory agents.

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

BIOMARKERS AND COMPANION DIAGNOSTICS

4:15 Unique Biomarker Signatures Identified by Novel Quantitative Immunohistochemistry Algorithms Predict Response and Survival to PD-1 Blockers and Chemotherapy

Naveen_DakappagariNaveen Dakappagari, Ph.D., Senior Director, Protein and Immuno-Oncology Biomarker Development, Navigate Biopharma, a Novartis Company

Although PD-1/L1 axis-targeted therapies produce durable responses in a subset of patients, reliable tests predictive of anti-PD-1 responses have been elusive. This presentation will describe novel multiplexed immunohistochemistry algorithms quantifying two prominent mechanisms of immunosuppression and their clinical utility in metastatic melanoma patients (n > 150) treated with anti-PD1 and early stage lung cancer patients (n> 100) receiving adjuvant chemotherapy. Mechanistic and real world implications of these findings will be discussed.

4:45 Protein and Genomic Immune Biomarkers at the Chase of Maximal Sensitivity, Multiple Targets and Optimal Responses

Vasiliki_PelekanouVasiliki Pelekanou, M.D., Ph.D., Associate Research Scientist, Pathology, Yale University School of Medicine

Immunotherapy modern companion diagnostics are marked by the urging need for increased sensitivity for the detection of target biomarkers, the constellation of tumor and stromal cells participating in immunoediting, as well as their functional status. The double-edged interaction of tumor microenvironment with therapeutic regimens (conventional or immune-targeting) creates a dynamic continuum that needs close follow-up. The potential of protein vs. genomic approaches might not be equivalent in this era.

5:15 Co-Development Issues for Immunotherapy Companion Diagnostics

Arnold_GelbArnold Gelb, M.D., Clinical Advisor, EMD Serono, Inc.

Differences in regulatory pathways, development timelines and the progression of clinical studies create challenges when developing companion diagnostics for immunotherapies and associated combinations. This presentation will review these issues and outline possible strategies for successful co-development projects.

5:45 Close of Rational Combination Cancer Immunotherapy


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