Cambridge Healthtech Institute's 6th Annual

Rational Combination Cancer Immunotherapy

Data Drives Combinatorial Strategies and Successes

August 27-28, 2018


All agree that combination therapy is the future of anticancer therapy. Thus, numerous clinical studies are exploring the application of immunotherapies in combinations with traditional and experimental agents. Emerging results from these preclinical models and clinical trials demonstrate the need for data analytics to provide actionable answers for patients. CHI's 6th Annual Rational Combination Cancer Immunotherapy conference takes a forward-looking perspective on the design of drug products and treatment progressions and builds on the knowledge arising from these exploratory trials.


Final Agenda

MONDAY, AUGUST 27

7:30 am Registration & Morning Coffee

DATA INFORMS IMMUNOTHERAPY COMBINATIONS

8:25 Chairperson's Opening Remarks

Lei Zheng, MD, PhD, Associate Professor, Oncology and Surgery, Johns Hopkins University School of Medicine


8:30 FEATURED PRESENTATION: Rational Combination of Immunotherapy, It Is Science, Not Logic

Samir N. Khleif, MD, Director, The Loop Immuno-Oncology Lab, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center

Combination immunotherapy is becoming the cornerstone of therapeutic approaches in cancer patients. Hundreds of combination immunotherapeutic clinical trials are being conducted nationwide and many of them are failing. Designing combination immunotherapy is not a simple endeavor and is not a straightforward addition of different agents. The tumor microenvironment is a complexed biologic system and designing clinical combinations has to take into account the complexity of its biology and the responsiveness of each of its components to the parts of the combination. Accordingly, proper design is crucial for the success of the therapy and should be fully dependent on biologic rational. We have identified certain biologic trends in rational combination and in what can work and why certain combination.

9:00 Hypomethylating Agents in Combination with Immune Checkpoint Inhibitors in Acute Myeloid Leukemia and Myelodysplastic Syndromes

Naval Daver, MD, Associate Professor, Leukemia Department, MD Anderson Cancer Center

Immune checkpoint inhibitors, as single-agent therapy, have shown modest clinical efficacy in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Hypomethylating agents (HMAs) such as azacitidine, while enhancing anti-tumor immune response, concurrently dampen immune response by upregulating inhibitory immune checkpoint molecule expression. Immune checkpoint molecule upregulation may be an important mechanism of azacitidine resistance. These findings have resulted in multiple clinical trials combining HMAs with immune checkpoint blockade. Clinical trial data have shown encouraging response rates and durable responses without resorting to stem cell transplant. In this presentation, we discuss preclinical and clinical trials investigating HMA-immune checkpoint inhibitor combinations in AML/MDS.

9:30 Rational Combination of PD-L1/PD1 Targeting and Natural Killer Cells: Hepatocellular Carcinoma Preclinical Study

Siu Tim Cheung, PhD, Associate Professor, Department of Surgery, The Chinese University of Hong Kong

Natural killer cells are increasingly used in the treatment of hematologic malignancy but vague efficacy in solid tumors. The present study provides data to improve the treatment response of PD-L1/PD1 targeting, and furthermore, to exploit the potential use of adoptive NK cells in immunotherapy. The data from the present study will facilitate rational design on combination therapy to improve survival outcomes of the aggressive tumors.

10:00 Coffee Break

10:30 Multiple "Immune Defects" in Pancreatic Cancer: How Do We Find the Right Combination of Immunotherapy?

Lei Zheng, MD, PhD, Associate Professor, Oncology and Surgery, Johns Hopkins University School of Medicine

The resistance of pancreatic cancer to immunotherapy could be caused by one or more of the four immune "defects" including lack of "high quality" T cells, stromal barriers to T cells getting access to tumor cells, immunosuppressive cells, and immune checkpoints in the tumor microenvironment of pancreatic cancer. To overcome such a resistance, a rational combination of agents that target multiple immune defects is highly demanded.

11:00 A Novel 3D Ex Vivo Platform of Fresh Patient Tumor Tissue for Immuno-Oncology Drug Development

Soner Altiok, CSO, Nilogen Oncosystems

Nilogen's novel 3D-EXSM drug assay utilizing fresh patient tumor samples with intact immune microenvironment can help facilitate oncology drug development and biomarker discovery. Our preclinical model recapitulates the complexity of tumor immune microenvironment to test the therapeutic potential of immuno-oncology drugs, identify rational combination therapies and develop novel predictive biomarkers.

11:15 Sponsored Presentation (Opportunity Available)

11:30 PANEL DISCUSSION: How Do We Find the Right Combination of Immunotherapy?

Moderator: Lei Zheng, MD, PhD, Associate Professor, Oncology and Surgery, Johns Hopkins University School of Medicine

As the discovery of new cancer immunotherapies continues to grow, developers are identifying promising patient-specific neoantigens and finding new ways to modulate the immune response beyond or in combination with checkpoint inhibitors. Panelists discuss what we know and where to go next.

12:00 pm Luncheon Presentation: Insights from Profiling the Tumor Microenvironment of Over 200+ Single Cell Tumor Suspensions

Shawn Fahl, PhD, Senior Research Associate, Research & Development, Folio Conversant

The cellular composition of the tumor microenvironment differs across indications and patients. The variability observed in immune cell infiltrates can be an important consideration when developing the next-generation of immunotherapies. As a high volume supplier of dissociated tumor cells, we have performed flow cytometric profiling on over 200 unique patient samples across multiple indications. This presentation will cover the insights and trends observed.

12:30 Session Break

LEVERAGING TRANSLATIONAL DATA FROM THERAPY RESPONSE

1:25 Chairperson's Remarks

Sarah Javaid, PhD, Associate Principal Scientist, Genetics and Pharmacogenomics, Merck

1:30 Forward and Reverse Translational Approaches to Augment Response to Anti-PD1 Therapy

Sarah Javaid, PhD, Associate Principal Scientist, Genetics and Pharmacogenomics, 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 who 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.

2:00 Leveraging Clinical and Preclinical Targeted Therapy Biomarker Data to Inform Combinations with Immunotherapy

Matthew Meyer, PhD, Senior Investigator II, Oncology Pharmacology, Novartis Institutes for BioMedical Research, Inc.

2:30 Sponsored Presentation (Opportunity Available)

3:00 Breakout Discussion Groups and Refreshment Break

This session features discussion groups that are led by a moderator who ensures focused conversations around the key issues listed. Attendees choose to join a specific group, and the small, informal setting facilitates sharing of ideas and active networking. Details on the topics and moderators are available on the conference website.

4:15 Precision Cancer Medicine in the Era of Genomics and Immunotherapy

Shumei Kato, MD, Assistant Clinical Professor, Experimental Therapeutics, GI Medical Oncology & Rare Tumor Clinic, Division of Hematology & Oncology and Center for Personalized Cancer Therapy, UC San Diego Moores Cancer Center

Although immunotherapies can demonstrate salutary anti-cancer effect in a portion of patients, unfortunately not all patients benefit. Even in the presence of favorable response markers (e.g., positive PD-L1, MSI-high, high tumor mutation burden), the response rate is about 50-60%. Further, some patients, e.g., some of those with MDM2 or EGFR alterations, may experience hyperprogression. We present our preliminary experience using a customized targeted and immunotherapy approach in cancer patients. Thus, further evaluation of immune biomarkers as well as novel combination strategy are required.

4:45 The Combination of a Non-Toxic Small Molecule IO Drug with Anti-PD1

Floyd Taub, MD, CEO & CMO, AxImmune

AxI 101 dramatically enhances the response of a variety of mouse models to anti-PD1. It modulates a variety of markers in animals, human PBMCs ex vivo and people in Phase I/II trials. All non-anergic lymphoma patients met irRECIST criteria for benefit. Markers determining success will be discussed.

5:15 Single Cell Immunoproteomes and AI-Supported Analysis to Predict Response to Immunotherapy

Carsten Krieg, PhD, Assistant Professor of Immunology, Microbiology & Immunology and Dermatology, Medical University of South Carolina

Immunotherapy has revolutionized oncology but not everyone responds to or relapses under therapy. Most likely, a combination of several therapeutics is needed to achieve tumor control. We developed a workflow based on high-dimensional single cell mass cytometry combined with artificial intelligence supported bioinformatics to analyze liquid blood biopsies to predict immune cell biomarkers. The generated "immune instagrams" might help in stratifying patients prior to immunotherapy, choose the right therapeutic combination, and help support clinical trial decisions.

5:45 End of Day

TUESDAY, AUGUST 28

7:30 am Morning Coffee

Deciphering Cancer's Dynamics and Immune Response

8:25 Chairperson's Remarks

Doron Levy, PhD, Professor, Department of Mathematics, University of Maryland

8:30 Leveraging Systems Biology and Machine Learning to Improve IO Biomarkers and Inform Combination Therapies

Janusz Dutkowski, PhD, CEO, Data4Cure, Inc.

A key challenge in the field of immunotherapy is predicting which patients will respond to IO therapy either as a single agent or in combination with other treatments. Existing clinical and research strategies, while informative, do not fully explain patient responses. Can a systems approach be more effective? How can we start to build a more comprehensive data-driven picture of the tumor-immune interaction system? The talk focuses on new methods, strategies, and platforms that may help in addressing these challenges.

9:00 Translational Immuno-Oncology in the Age of Big Data - A Bioinformatics Perspective

Yuriy Gusev, PhD, Associate Professor, Innovation Center for Biomedical Informatics (ICBI), Georgetown University

A field of Immuno-Oncology is evolving toward utilization of big data generated by genomic technologies. Many companies and academic research centers have started to adapt bioinformatics methods and tools to deal with the sudden influx of large volumes of molecular profiling data such as genomic sequencing and other omics technologies. A broad overview will be presented of bioinformatics resources and trends for Immuno-Oncology applications, with examples of bioinformatics solutions for translational immune-oncology based on recent collaborations at Georgetown Medical Center.

9:30 Clinical Intelligence-Driven Combination Prediction: A Machine Learning Approach

Nandu Gattu, PhD, Senior Vice President, Pharma Analytics, Excelra Knowledge Solutions

The expansive landscape of cancer immunotherapies presents vast clinical data, however, the challenge is to find comprehensive clinical trial intelligence with granular information to predict clinical outcomes and design studies. In this talk, we will present a case study on identification of potentially successful drug combinations using our proprietary clinical trials platform. The machine learning-based pathway synergy analysis is combined with systems-level biological interpretation to establish the mechanistic role of the combination in cancer immunotherapy.

10:00 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

10:55 Chairperson's Remarks

Doron Levy, PhD, Professor, Department of Mathematics, University of Maryland

11:00 A Dynamic View of Cancer Dynamics and Drug Resistance

Doron Levy, PhD, Professor, Department of Mathematics, University of Maryland

Cancer can (and should) be viewed as a very complex and heterogeneous dynamical process. A quantitative realization of the dynamics of the disease may assist in effectively combating it. In this talk we describe how mathematical tools can be used to study cancer dynamics and how this knowledge can be quantitatively utilized to design therapies.

11:30 Tumor Analytical Methods: Profiling by Gene Cluster Summary Scores (GCESS)

Jaime F. Modiano, VMD, PhD, Perlman Professor of Oncology and Comparative Medicine, Veterinary Clinical Sciences, College of Veterinary Medicine and Masonic Cancer Center, University of Minnesota

The GCESS method can differentiate tumors of different histologic origins into prognostically significant subtypes. Gene clusters are defined based on statistical correlations, including parameters that define intrinsic tumor behaviors as well as the composition of the microenvironment and the immunological landscape. The pattern of expression for these clusters is highly conserved across species, reflecting the biology of the disease and underscoring its utility for predicting tumor behavior and metastatic propensity.

12:00 pm Close of Rational Combination Cancer Immunotherapy

* The program is subject to change without notice, due to unforeseen reason.

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