Immuno-Oncology Biomarkers and Companion Dx

Recent advances in cancer immunotherapy have generated excitement across all fields of oncology. When working, immune checkpoint inhibitors and adoptive T-cell therapies create more sustainable results with less probability of recurrence than conventional or targeted cancer therapy. However, the field is still experiencing a lack of predictive biomarkers and companion/complementary diagnostics. Challenges in discovering predictive biomarkers for cancer immunotherapy involve multiple cell types, multiple mechanisms of T-cell regulation, genetic heterogeneity of tumors, immune components, etc. The companion and complementary diagnostics for immune modulating therapies are complicated and require a new systematic approach. Cambridge Healthtech Institute’s Inaugural Immuno-Oncology Biomarkers and Companion Dx conference is designed to bring together clinical immuno-oncologists, researchers from pharmaceutical companies and members of the laboratory medicine community to discuss the underlying mechanisms of cancer immunotherapy, its predictive biomarkers as well as existing and emerging clinical assays aiming to improve patient outcomes.

Monday, February 12

10:30 am Conference Program Registration Open

KEYNOTE SESSION: PRECISION MEDICINE IN IO

11:50 Chairperson’s Opening Remarks

Zhen Su, M.D., MBA, Chief Medical Officer, North America, EMD Serono

12:00 pm Predictive Biomarkers and Companion Diagnostics: The Next Wave

Ron Mazumder, Ph.D., MBA, Vice President and Global Head of Oncology, Biomarker Development and Companion Diagnostics, Genentech

I will discuss new predictive biomarkers and companion diagnostics platforms that are currently being explored or developed as companion diagnostics across our immuno-oncology, oncology and hematology programs.

12:30 Precision Medicine for Immuno-Oncology: Insights into Recent Biomarker Advancements

Zhen Su, M.D., MBA, Chief Medical Officer, North America, EMD Serono

With IO therapies rapidly evolving, the question still remains, which patients will respond? IO has changed the treatment landscape significantly, however, the respective biomarkers and diagnostics do not yet provide a clear direction for clinicians to identify the responsive patient sub-populations. From tumor associated PD-L1 expression, to T-cell infiltrates and mutational burden, we will review the current and future trends as well as discuss the challenges for IO biomarker biology.

1:00 Session Break

1:10 Luncheon Presentation I: Profiling the Changing Immune Infiltrates During Neoadjuvant Therapy For Soft-Tissue Sarcomas

Seth Pollack, M.D., Assistant Member, Fred Hutchinson Cancer Research Center, Clinical Research Division; Assistant Professor, University of Washington, Division of Oncology, Fred Hutchinson Cancer Research Center

Sarcomas are a group of >70 cancers of mesenchymal origin together comprising ~1% of all cancers. Even with state-of–the-art care, >50% of patients with large, high grade tumors develop advanced disease. Immunotherapy has great potential, but little is known about the changing immune microenvironment. Using multiple approaches, including Cofactor Genomics’ Paragon assay, we have generated a molecular profile of these cancers, to better understand the changing immune TME in soft tissue sarcoma during neoadjuvant therapy.

1:40 Session Break

FROM BIOMARKER DISCOVERY TO COMPANION DIAGNOSTICS

2:30 Chairperson’s Remarks

Robert D. Loberg, Ph.D., Executive Director of Clinical Biomarkers & Diagnostics, Amgen, Inc.

2:40 Approaches to Discovery & Development of Immuno-Oncology Biomarkers

Robert D. Loberg, Ph.D., Executive Director of Clinical Biomarkers & Diagnostics, Amgen, Inc.

The integration of a comprehensive immune-oncology biomarker and diagnostic strategy is a crucial component of the drug development process. Three key areas of focus include 1) the development of a biomarker and diagnostic strategy early, 2) enabling early biomarker efforts in pre-clinical and clinical development, and 3) the successful execution of biomarker and diagnostic driven clinical development programs.

3:10 The Parker Institute’s Collaborative and Integrated Approach to Immuno-Oncology Biomarkers

Theresa LaVallee, Ph.D., Head of Translational Medicine, The Parker Institute for Cancer Immunotherapy

The Parker Institute for Cancer Immunotherapy’s mission is to accelerate the development of breakthrough immune therapies to turn cancer into a curable disease. Through collaborative efforts utilizing innovative technologies and integrating clinical and correlative datasets, Parker is advancing the understanding and utilization of immuno-oncology biomarkers.

3:40 High Definition Multiplexing for Biomarker Discovery

Stephanie Walter, Ph.D., R&D Team leader, Ultivue
Biomarker discovery in immuno-oncology requires the analysis of multiple protein markers (n>4) with their spatial relationships at an amenable throughput. The scrutiny of the tumor micro-environment demands whole-slide multiplexed images featuring immune and tumor cells. Ultivue's InSituPlex platform fulfills this need with the data reproducibility relevant to CDx.

4:10 How to Accelerate the Development of Biomarkers through Consortia: Application to Immuno-Oncology

Vanessa Tumilasci, Ph.D., Project Director, Trans-Hit Bio

4:25 PANEL DISCUSSION: Integrated Approaches to IO Biomarkers and Companion Dx

Moderator: Robert D. Loberg, Ph.D., Executive Director of Clinical Biomarkers & Diagnostics, Amgen, Inc.

Panelists: Theresa LaVallee, Ph.D., Head of Translational Medicine, The Parker Institute for Cancer Immunotherapy

Seth Pollack, MD, Assistant Member, Fred Hutchinson Cancer Research Center, Clinical Research Division; Assistant Professor, University of Washington, Division of Oncology, Fred Hutchinson Cancer Research Center

Zhen Su, M.D., MBA, Chief Medical Officer, North America, EMD Serono

  • Latest advances in overcoming tumor-induced immune suppression and immune escape
  • Standardization of existing assays and approaches
  • Clinical trials for cancer immunotherapy: specific features and the role of diagnostics

4:40 Refreshment Break and Transition to Plenary Session

5:00 Plenary Keynote Session (click here for more details)

 

Precision for Medicine

 6:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing

7:30 Close of Day

Tuesday, February 13

7:30 am Registration Open and Morning Coffee

8:00 Plenary Keynote Session (click here for more details)

9:00 Refreshment Break in the Exhibit Hall with Poster Viewing

PATIENT SELECTION IN CLINICAL TRIALS

10:05 Chairperson’s Remarks

Paul Robbins, Senior Director, Early Development and Translational Oncology, Pfizer

10:15 Translational Strategies for Development of I/O Combinations

Paul Robbins, Senior Director, Early Development and Translational Oncology, Pfizer

Full realization of the promise of immunotherapy will require knowledge and understanding of an individual’s disease and the coordinated use of therapies which address both the underlying mechanisms driving tumorigenesis as well as those limiting immune recognition or the formation of productive responses. Within the diverse and expanding range of I/O combinations in development, an essential element for success is the determination of which target(s), mechanism(s) or biomarker(s) should be prioritized to define the most appropriate patient population in which to test a given treatment.

10:45 Biomarker Management in Immuno-Oncology Clinical Trials

Maria Tverskoy, Ph.D., Biomarker Operations Program Leader, Product Development Global Operations, Genentech

Clinical trials are becoming more complex by shifting to personalized medicine, looking at mechanisms of actions of immuno-oncology (I-O) agents and evaluating responses to new immunotherapy combinations. Inclusion of biomarkers has been critical to understanding the underlying biological response in clinical trials. This talk will focus on specific challenges in biomarker management and strategies that can be used for successfully operationalizing biomarker assessments in I-O clinical trials.

 Omniseq11:15 Comprehensive Immune Profiling for Immunotherapy Treatment Decision Support

Mark Gardner, CEO, OmniSeq Inc.
There are a number of biomarkers used today – MSI, PD-L1 IHC, mutational burden – for considering patients for immunotherapy.  When used individually, these biomarkers each have challenges: some biomarkers are prevalent, but not highly correlated with response.  Other biomarkers are not prevalent (~5%), but are correlated well with response.  This presentation reviews the Immune Report Card, a multi-modality assay that synthesizes 5 different tests to present the most comprehensive immune profile available today.

Cell Dx  11:45 High Throughput Multiplex Immunofluorescence for Immuno-Oncology

David Schwartz, Ph.D., CEO/CSO, Cell IDx, Inc.

To fully understand the effect of immune cells in the tumor microenvironment requires multiple complex steps including staining, imaging and image analysis. Here we present a simple high throughput technology that allows simultaneous, sensitive and specific detection of immune markers.

Precision for Medicine12:00  pm  Combination IO Therapies Need a Next Generation Tool to Measure Responses 
Thomas O Kleen, Ph.D., Vice President, Immune Monitoring and Specialty Lab Services, Precision for Medicine
Monitoring both systemic changes in the blood and TILs will be essential for current and next generation Immunotherapy trials. Logistics, quantity requirements, stability of cells in blood samples and tissue often preclude the use of standard monitoring assays in large trials. Next generation Epiontis ID allows samples to be simply frozen on-site and easily shipped without any burden on clinical sites. Only 75ul-300ul of whole blood or small amounts of tissue allow for precise and robust quantification of immune cells in all human samples. Tregs, Th17, Tfh, CD3+, CD4+, CD8+, B, NK and PD-1 positive cells are the first examples of next generation monitoring tools for immuno-oncology trials.

12:15 Session Break

MolecularMD  12:25 Luncheon Presentation I: Mitigating Risk when Navigating the Journey from Biomarker Validation to the Commercial Deployment of a CDx

Cindy Spittle, Ph.D., Vice President, Development and Scientific Affairs, MolecularMD

Multiple biomarker assays and methodologies are being developed for use in I/O POC studies. Technical, regulatory and operational factors need to be evaluated when selecting a platform and assay that can be successfully implemented in a clinical trial and ultimately approved as a complementary or companion diagnostic. Insights and examples will be provided on how to effectively manage a co-development project starting in Phase 1/2 trials through approval and commercial implementation of a CDx.  

 Oxford Biodynamics 12:55 Luncheon Presentation II: Looking Past IHC and Digital GEX for Immune-oncology Biomarkers: EpiSwitch™

Alexandre Akoulitchev, MA, Ph.D., FRSM, CSO, Oxford Biodynamics Plc

In development of predictive IO biomarkers and CDx the default strategies based on established platforms have faced lately a number of challenges. Oxford Biodynamics has deployed 3D genome regulatory architecture as an essential part of phenotype stratification: using data from 3 independent studies based on 2 different anti-PD-L1 therapies and 1 anti-PD-1 therapy, the results show high consistency and disseminating powers for non-invasive precision biomarkers for the IO field with EpiSwitch™ Technology Platform.

1:25 Refreshment Break in the Exhibit Hall with Poster Viewing

NEOANTIGENS AND TUMOR MUTATION BURDEN

2:00 Chairperson’s Remarks

Terri McClanahan, Ph.D., Executive Director, Profiling & Expression, Translational Medicine, Merck Research Laboratories

2:10 Predictive Biomarkers of Response to Anti-PD1 Therapy

Terri McClanahan, Ph.D., Executive Director, Profiling & Expression, Translational Medicine, Merck Research Laboratories

Pan-cancer molecular biomarkers of immunotherapy response may be important for identifying patients likely to derive benefit from PD-1/PD-L1-directed monotherapy, while also proving useful for guiding the rational use of combination immunotherapy regimens. Data will be presented showing that somatic mutational load (ML) and a T-cell inflamed gene expression profile (GEP) are key determinants and independent predictors of response to pembrolizumab across multiple tumor types.

2:40 Natural Variation in Innate Immune Cell Parameters Is Driven by Genetic Factors

Matthew Albert, Ph.D., Principal Scientist, Cancer Immunology, Genentech

Enumeration and characterization of circulating immune cell populations provide key indicators of human health and disease. To identify environmental and genetic factors driving innate and adaptive immune cell parameters in homeostatic conditions, we combined semi-automated flow cytometric analysis of blood leukocytes and genome-wide DNA genotyping in 1,000 healthy, unrelated individuals of western European ancestry.

3:10 Neoantigen Scores to Guide Personalized Cancer Immunotherapy

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

Increasing the number of patients that respond successfully to cancer immunotherapies is the next big step in the fight against cancer. Recent studies have shown that the more tumor-specific mutations, or neoantigens, the cancer cells have, the greater the chance that the tumor will not be tolerated by the immune system.

RareCyte 3:40 Circulating Rare Cell Biomarkers for Immuno-Oncology
Eric Kaldjian, CMO, RareCyte, Inc
Using the RareCyte platform, we developed a 6-parameter CTC assay that allows simultaneous assessment of PD-L1 and Interferon Regulatory Factor-1. In addition, we used the platform to identify rare circulating tumor antigen-specific T cells and show that 6-color imaging allows us to identify a subset consistent with an exhausted phenotype. Retrieval of rare antigen-specific T cells using the integrated CytePicker module would be important for biomarker discovery tool as well as TCR discovery against neoantigens.

4:10 Valentine’s Day Celebration in the Exhibit Hall with Poster Viewing

5:00 Breakout Discussions in the Exhibit Hall

These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

Gaps and Opportunities in Biomarker Development for IO Therapies

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

  • Need for longitudinal monitoring of immune response
  • Deeper understanding of PDx mechanisms of treatment resistance
  • Identifying biomarkers for combination drug development

Tumor Mutation Burden as an IO Biomarker

Terri McClanahan, Ph.D., Executive Director, Profiling & Expression, Translational Medicine, Merck Research Laboratories

  • What is the likelihood of immunotherapy working in tumors with low tumor mutational burden (Pancreatic, GBM)?
  • If not checkpoint inhibitors, what are the best immunotherapy-related therapeutic strategies in these tumor types?
  • What is the clinical utility of circulating tumor DNA (ctDNA) vs tumor DNA to measure tumor mutational burden?
  • What are the thoughts on a future landscape with a dual biomarker (one for each axis, Inflammation/Neoantigens)?

6:00 Close of Day

Wednesday, February 14

7:30 am Registration Open and Morning Coffee

8:00 Plenary Keynote Session (click here for more details)

10:00 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall

BIOMARKER STRATEGIES FOR COMBINATION THERAPIES

10:50 Chairperson’s Remarks

Scott D. Patterson, Ph.D., Vice President, Biomarker Sciences, Gilead Sciences, Inc

11:00 High-Content Molecular Profiling in Development of Combination Immunotherapies: Making Rational from Non-Rational

Ruslan Novosiadly, Ph.D., Senior Research Advisor, Cancer Immunobiology, Biomarkers, Eli Lilly

Biomarker discovery paradigm in immuno-oncology has been shifting from hypothesis-testing to hypothesis-generating mode. High-throughput, high-content molecular and immune profiling enables comprehensive biomarker evaluation. Interrogation of mechanistic biomarkers in preclinical mouse tumor models helps identify and guide rational combinations in immune-oncology.

11:30 Next Generation Biomarkers for the Era of Combination Cancer Immunotherapies

Sarah Javaid, Ph.D., Senior Scientist, Discovery Pharmacogenomics, Genetics, 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 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 and identify predictive biomarkers for patients.

12:00 pm PANEL DISCUSSION: Biomarkers for Combination Cancer Immunotherapy

Moderator: Scott D. Patterson, Ph.D., Vice President, Biomarker Sciences, Gilead Sciences, Inc.

Panelists: Paul Robbins, Senior Director, Early Development and Translational Oncology, Pfizer

Mark Gardner, CEO, OmniSeq Inc.

Speakers of the Session

  • Current and emerging biomarkers for patient selection for immuno-oncology therapies – will current assays be completely superseded?
  • Beyond the biopsy - what future blood-based biomarkers?
  • NGS panels have arrived – are we ready for complex transcript panels?
  • Harmonization of multiple assays for the same biomarker(s) – can this be achieved during development?

12:30 Session Break

12:40 Enjoy Lunch on Your Own

1:10 Dessert Break in the Exhibit Hall and Last Chance for Poster Viewing

PATHOLOGY OFFERINGS

1:50 Chairperson’s Remarks

Cyrus Hedvat, Ph.D., M.D., Director, Pathology, Bristol-Myers Squibb

2:00 Are We There Yet? Quantitative Multiplexed Tissue Assay Development for Immuno-Oncology Clinical Trial Support
Jennifer Giltnane, M.D., Ph.D., Pathologist, Genentech
Supporting immuno-oncology programs has created opportunities for digital pathology and multiplex immunoassays to move into clinical trials in two ways: (1) we can use less tissue by combining analytes on one slide, and (2) we can enumerate and localize cellular populations of the tumor microenvironment in a way that other quantitative assays cannot. In the first case, programs of targeted combination therapies aim to drive the immune system into the tumor while simultaneously turning off the regulatory brakes. In order to confirm the mechanism of action, on-treatment needle core biopsies are necessary but provide very limited tissue for pharmacodynamic assays. In addition, multiplexed IHC can subset immune cells and measure their spatial relationship with each other and tumor cells, potentially providing answers to improve patient selection.

2:30 Manual Pathology Scoring in IO – Why Is It So Hard to Be the Gold Standard?

Famke Aeffner, D.V.M., Ph.D., Principal Pathologist, Comparative Biology and Safety Sciences, Amgen

In immuno-oncology, manual scoring of biomarker expression in tissues by pathologists is becoming a crucial factor in clinical trial patient selection, and companion and complementary diagnostic development. At the same time, meaningful scoring paradigms, especially of infiltrating lymphocytes, are challenging to apply in a reproducible and consistent manner. What are the factors that pose specific challenges to pathologists, and how can digital image analysis tools aid in overcoming these issues?

3:00 Immunohistochemical Tumor Profiling Using Combined Manual and Automated Image Analysis Approaches to Interpret Biomarkers in Immuno-Oncology

Cyrus Hedvat, Ph.D., M.D., Director, Pathology, Bristol-Myers Squibb

Identification of predictive biomarkers in the tumor microenvironment (TME) is critical to determine effective single and combination immunotherapy approaches. Immunohistochemistry (IHC) remains an important tool for characterization of biomarkers, but accurate and reproducible quantification of immune cells IHC assays remains a challenge. We demonstrate an effective method for interpretation of IHC immune biomarkers in a series of solid tumors by using both automated image analysis and manual pathologist scoring.

3:30 Session Break

CELL-BASED BIOMARKERS IN IO

3:40 Chairperson’s Remarks

Joseph A. Fraietta, Ph.D., Associate Director, Product Development, Center for Advanced Cellular Therapeutics, University of Pennsylvania

3:45 Changes in Circulating Leukocyte Quantities Inform Dosing Decisions and Pharmacodynamic Effects in Combination Trials of Immune Oncology Therapeutics

Nathan Standifer, Ph.D., Senior Scientist, Clinical Pharmacology and DMPK, MedImmune

Immune oncology (IO) therapeutics are designed to activate exhausted T cells, thereby enhancing tumor-specific immune responses. While IO compounds have demonstrated substantial efficacy, most treated patients fail to respond. As such, trials of IO therapeutics combined with small molecule inhibitors have been undertaken. This presentation will describe the use of flow cytometry-based assays to monitor circulating leukocyte populations to characterize pharmacodynamic effects and inform dosing decisions in such combination trials.

4:15 Beyond Uni-Variate Analyses Using Cytometry Data - Translation into Clinical Space

Iulian Pruteanu-Malinici, Ph.D., Biostatistics, Investigator II/Lab Head at Novartis Institutes for BioMedical Research (NIBR)

Here, we present a flow cytometry based framework that, when combined with state of the art bioinformatics, enables for the discovery of biomarkers that predict clinical response of CTL019 therapeutic products. The aim is to identify a biomarker signature that correlates with clinical response; to measure the predictive power of each signature, a T-test is used to evaluate the difference between measured phenotypes’ cell frequencies (the number of cells in that phenotype divided by the total number of cells in the parent population) among Complete Responders (CR) and Non-Responders (NR). The most statistically significant phenotypes are then selected for manual confirmation using FlowJo.

4:45 Biomarkers for CAR T Cell Therapy and Combinations

Joseph A. Fraietta, Ph.D., Associate Director, Product Development, Center for Advanced Cellular Therapeutics, University of Pennsylvania

Chimeric antigen receptor (CAR) T cells that target tumor antigens can induce remissions in patients with hematologic malignancies, but only in a subset of subjects with CLL. The mechanisms that potentiate CAR T cell potency are largely unknown. Here we describe a remarkable case that helps clarify determinants of persistence and points to a modifiable epigenetic pathway which may increase anti-tumor activity and therapeutic efficacy of gene-modified T cells.

5:15 Close of Conference Program


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