Cambridge Healthtech Institute’s Third Annual

Biomarkers for Cancer Immunotherapy

Next-Generation Biomarkers for Combination Therapies: Beyond PD-1 and PD-L1

February 23-24, 2017 | Moscone South Convention Center | San Francisco, CA
Part of the 24th International Molecular Medicine Tri-Conference

 

As results from immunotherapy trials roll in, new biomarkers are being proposed, including inflammatory cell features, tumor mutational burden, gene expression profiles, and the presence of DNA repair defects. Still, additional biomarkers are needed to prioritize and tailor patient treatment so that combination therapies can be used for patients with poor response to traditional therapies. PD-1 and PD-L1 are establishing themselves accepted biomarkers for cancer immunotherapies, but research is moving beyond checkpoint inhibitors and into co-stimulatory agents and cellular therapies. Cambridge Healthtech Institute’s Third Annual Biomarkers for Cancer Immunotherapy symposium will provide a forward-looking perspective at the diagnostics side of immune-oncology. Speakers will address the development of predictive and prognostic IO biomarkers, utility of these biomarkers in clinical trials, and their potential as companion diagnostics. Overall, this event will provide solutions to bridge the gap between biomarkers and therapy selection and monitoring.



Thursday, February 23

7:00 am Registration and Morning Coffee

BIOMARKER STRATEGIES FOR COMBINATION THERAPIES

8:25 Chairperson’s Opening Remarks

Robert Anders, M.D., Ph.D., Associate Professor, Pathology, Johns Hopkins

8:30 Biomarker Strategies for Cancer Immunotherapy Combination Studies

Jeffrey Wallin, Ph.D., Group Leader and Senior Scientist, Oncology Biomarker Development, Genentech, Inc.

The detection and destruction of malignant cells by cytolytic T effector cells is a hallmark of cancer immunotherapy. Although durable responses have been observed with immune checkpoint blockade in some cancers, combination approaches will be required to extend this benefit beyond a subset of patients. Combinations for cancer immunotherapy involve promotion of one or more steps of the cancer-immunity cycle and biomarkers can provide valuable diagnostic and mechanistic information for cancer immunotherapy clinical trials. This talk will focus on biomarker strategies that can be utilized to inform decision-making in cancer immunotherapy clinical trials.

9:00 Development of a Potential Companion Diagnostic (CDX) for Pembrolizumab on the Nanostring Ncounter® Dx Analysis System

Matt Marton, Ph.D., RAC, Director, Genomics and Companion Diagnostics, Translational Biomarkers, Merck & Co., Inc.

We describe the development of a gene expression biomarker that correlates with response to pembrolizumab in multiple cancer types. The 18-gene signature includes genes involved in cytokine signaling, antigen processing and immune checkpoint regulation. We will discuss analytical performance characteristics of the assay under investigation as a diagnostic device in multiple protocols in multiple indications for its ability to identify responders to pembrolizumab treatment.

9:30 Detecting Resistance before RECIST: The Role of Tumor Biomarkers in Immunotherapy

Morganna Freeman, D.O., Associate Director, Melanoma and Cutaneous Oncology Program, The Angeles Clinic and Research Institute

Over the last few years, immune-based cancer therapies have dramatically altered the treatment landscape in oncology. On the heels of those breakthrough therapies is intense immunoprofiling to predict and prognosticate clinical responses, however the immune system is just one half of the equation. Cancer biomarkers to detect adaptive resistance and early relapse have an emerging role in immunotherapy, the development and utilization of which will be discussed in detail here.

10:00 Simoa for the Ultra-Sensitive Measurement of Proteins as Biomarkers of Immuno-Oncology Therapeutics

David Duffy, Massachusetts Vice President, Research and Chief Technology Officer, Quanterix Corporation

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.



10:15 Sponsored Presentation (Opportunity Available)

10:30 Coffee Break with Exhibit and Poster Viewing

PD-1 AND PD-L1: FUTURE DIRECTIONS

11:15 Biomarkers in the Tumor Microenvironment: What Is Working and How Can We Do Better?

Robert Anders, M.D., Ph.D., Associate Professor, Pathology, Johns Hopkins

This lecture will discuss the status of immune based therapies and the state of the art in using predictive biomarkers to guide therapy. The use of PD-L1 as a biomarker will be discussed in the context of the tumor immune microenvironment. The results and interrogation of the colon cancer tumor microenvironment will also be summarized.

11:45 PD-1 and PD-L1 Blockade – Step 1. Bringing Immunotherapy to the Masses

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

Blocking either the PD-1 receptor or its ligand PD-L1 has improved overall survival in Phase III trials in patients with melanoma, kidney cancer, and non-small cell lung cancer. Current clinical trials are investigating the toxicity and efficacy of combining PD-1 pathway blockade with other therapies, since the majority of patients fail to respond to PD-1 pathway blockade. However, a subset of patients develop significant, durable benefits from PD-1 pathway monotherapy.

12:15 pm Sponsored Presentation (Opportunity Available)  

12:30 Session Break

12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Session Break

CLINICAL CASE STUDIES

 2:25 Chairperson’s Remarks

Bernard A. Fox, Ph.D., Providence Cancer Center

2:30 Strategies to Induce and Monitor Anti-Cancer Immunity in Patients with Non-Small Cell Lung Cancer (NSCLC).

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

Patients who fail checkpoint blockade are thought to lack T cells capable of recognizing a broad spectrum of antigens expressed by all cancer cells. To address this hurdle we have developed a DC-targeted microvesicle cancer vaccine, DPV-001, that contains > 100 proteins over-expressed by NSCLC. Results of a Phase II study of DPV-001 in patients with NSCLC, document induction and/or boosting of immune responses against cancer antigens in every patient. Monitoring strategies employed and opportunities to stratify patients for next generation trials will be discussed.

3:00 The Novel Phase 2 Immunotherapeutic, Imprime PGG, Repolarizes the Tumor Immune Microenvironment and Activates Antigen Presentation to Drive an Integrated Anti-Cancer Immune Response with Checkpoint Inhibitors

Jeremy Graff, Ph.D., CSO, Senior Vice President, Research, Biothera Pharmaceuticals, Inc.

Imprime PGG is a systemically administered PAMP (Pathogen Associated Molecular Pattern) currently in phase 2 trials. As a PAMP, Imprime PGG binds directly to innate immune cells, triggering a cascade of immune activating events. These include the repolarization of the immune suppressive myeloid cells within the tumor microenvironment as well as the activation and maturation of dendritic cells, the immune system’s professional antigen presenting cells. As a consequence, Imprime PGG treatment effectively stimulates T cell activation and synergizes with immune checkpoint inhibitors to enhance anti-tumor efficacy in multiple pre-clinical tumor models. A recently completed phase 1 study in healthy human volunteers has shown that Imprime PGG- mediated immune activation requires immune complex formation with naturally occurring anti-beta glucan IgG antibodies (ABA), levels of which vary across the human population. These ABA are now being used to pre-select patients for inclusion in a series of phase 2 studies in combination with pembrolizumab.

3:30 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall

BEYOND CHECKPOINT INHIBITION: WHERE DO WE GO FROM HERE?

4:15 Utility of Teff Signature Assays in Plasma to Measure Pharmacodynamic Changes in Phase 1 Study of Atezolizumab and Cobimetinib in Melanoma

Vinita Gupta, Ph.D, Scientist, Cancer Immunotherapy, Genentech

As an exploratory objective of this phase 1a study, profiling of T cell activation markers was carried out in plasma of melanoma patients (n=22) at baseline and post dose that might act as indicators of immuno-modulatory effect of Cobimetinib with Atezolizumab. We qualified immunoassays for Teff signature panel as well as other immune-monitoring markers such as CCL2, IL-6, IL-18 and TNF-a on Simple-Plex and Quanterix platforms to study harmacodynamics of this drug combination. The assays exhibited CV<20% and accuracy within 70-130% range. The majority of patients show a spike in Teff signature markers at Cycle 1 Day 15 of the treatment as a pharmacodynamic response and suggesting a mechanism of action for these drugs.

4:45 Liquid Biopsies in Immuno-Oncology Drug Development

Shidong Jia, Ph.D., Founder & CEO, Predicine

Cancer immunotherapy offers great promise where biomarkers have been shown to predict therapy outcome in various types of cancer patients. The talk will describe the development of a next-generation sequencing-based liquid biopsy test to support drug development in cancer immunotherapy clinical trials.

5:15 Objective Measurement and Significance of IDO1, B7-H3 and B7-H4 in Hormone Receptor-Positive Breast Cancer

Daniel E. Carvajal-Hausdorf, M.D., Postdoctoral Associate, Pathology, Yale School of Medicine

Immunostimulatory therapies targeting immune suppressive pathways produce durable clinical responses in advanced solid tumors. However, PD-1/PD-L1 axis blockade has been in ineffective in hormone receptor positive breast cancer (HR+ BC). Here, we objectively assessed the expression of immunomodulatory enzyme IDO1 and immune checkpoint molecules B7-H3 and B7-H4, and their relationship with tumor-infiltrating lymphocytes in HR+ BC

5:45 Reception with Exhibit and Poster Viewing

6:45 Close of Day

Friday, February 24

7:00 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

8:00 Registration Open

BEYOND CHECKPOINT INHIBITION (CONT.)

8:25 Chairperson’s Remarks

Sandip Patel, M.D., Assistant Professor, Cancer Immunotherapy Program, Experimental Therapeutics, Thoracic Oncology; Assistant Director, Clinical Trials Office, Medicine/Hematology & Oncology, University of California, San Diego Moores Cancer Center

8:30 Novel T Cell Biomarkers for Response to Immune Checkpoint Therapies

Adil Daud, M.D., HS Clinical Professor, Medicine (Hematology/Oncology), University of California, San Francisco; Director, Melanoma Clinical Research, UCSF Helen Diller Family Comprehensive Cancer Center

9:00 Beyond PD-L1 as a Biomarker for Checkpoint Inhibition

Arnold Gelb, Head, Companion Diagnostic Development & US Site Head, EMD Serono

After briefly reviewing the current status of PD-L1 as a biomarker and Companion Diagnostic, including the limitations thereof, an overview of other candidate biomarkers for checkpoint inhibition will be presented. This overview will include select aspects of the tumor microenvironment, immune cell phenotyping, T cell repertoires, IFN-gamma gene signature, neoantigen burden, MSI status, and possible other “hot topics” that have been described in the interim.

9:30 Next-Generation Cancer Immunotherapy: Agents and Biomarkers

Sandip Patel, M.D., Assistant Professor, Cancer Immunotherapy Program, Experimental Therapeutics, Thoracic Oncology; Assistant Director, Clinical Trials Office, Medicine/Hematology & Oncology, University of California, San Diego Moores Cancer Center

Dr. Sandip Patel, M.D. will be discussing predictive biomarkers for immunotherapeutic response in cancer, with a focus on novel biomarker assays. He will be focusing on the nuances in the development of PD-L1 IHC with a focus on alternative predictive biomarkers that may better determine patient response to immune checkpoint modulation. Additionally, Dr. Patel will be discussing the next generation of cancer immunotherapeutics currently under development including cell-based approaches.

10:00 Highly Multiplexed IHC Assays to Examine Immune Checkpoints and Biomarkers for Immunotherapy

Jennifer Ziello, Senior Research Associate, Translation Diagnostics, Cell Signaling

The emergence of an increasing number of immunotherapy biomarkers and the importance of their context within the tumor microenvironment has resulted in a need for high-plex immunohistochemistry (IHC) assays. Using highly specific and validated antibodies developed for this purpose, we constructed several fluorescent multiplexed, TSA-based assays to examine the frequency, spatial localization, and proximity of immune cells within the tumor microenvironment. Our data demonstrates the feasibility of simultaneous detection of seven fluorochromes in order to visualize immunosuppressive receptors associated with the exhausted T cell phenotype, myeloid-derived suppressor cells, and the PD-1:PD-L1 axis. Our findings demonstrate the utility of multiplex IHC to deconvolute protein expression and interactions within the complex tumor microenvironment.

10:30 Coffee Break with Exhibit and Poster Viewing

ESTABLISHING COMPANION DIAGNOSTICS ACROSS TARGETED IMMUNOTHERAPIES

11:15 Precision Immunotherapy: The Challenge of Converting Complex Predictive Biomarkers into Practical Companion Diagnostics

Kenneth Emancipator, M.D., Executive Medical Director, Translational Medicine, Companion Diagnostics, Merck & Co.

Early immunotherapies have produced dramatic results for some patients, but future immunotherapies likely need to be guided by diagnostics to benefit more patients. Properly targeting immunotherapy requires incorporating into clinical practice complex diagnostics which can assess host immune response in addition to cancer biology itself. “Precision Immunotherapy” requires discovery of appropriate predictive biomarkers and incorporating them into practical companion diagnostics which will be adopted by practitioners.

11:45 Establishing Companion Diagnostics for Immunotherapies Including OPDIVO® (Nivolumab)

Neeraj Adya, Ph.D., Director, Pharmacodiagnostics Research and Development, Bristol-Myers Squibb

Clinical utility of single biomarker-based companion diagnostics (CDx) to select patients has been effectively demonstrated for mutation targeted therapies. An effective CDx for immunotherapies like OPDIVO® will likely require a set of biomarkers that serves as a surrogate for identifying immune status in patients. These biomarkers will need to meet the same analytical rigor as for a single biomarker. This talk leverages lessons learned from PD-L1 towards future CDx development.

12:15 pm Companion & Complementary Diagnostic Strategies for Cancer Immune Therapies

J Andrew Williams, Ph.D., CDx Franchise Leader, Cancer Immune Therapies, Genentech

This presentation highlights diagnostic strategies for cancer immune therapies.  Based on a 2017 publication (Scheerens et al. 2017 Clinical and Translational Sciences, DOI:10.1111/cts.12455) considerations for companion and complementary diagnostics will be discussed with potential for broader application across other diseases. Relevant data from the 2016 approval of atezolizumab (Tecentriq) in NSCLC will be covered. Immunhistochemistry (IHC) and molecular assay data will be presented, along with key learnings from assay comparisons.

12:45 Close of Symposium


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