Recent advances in cancer immunotherapy have generated excitement across all fields of oncology. However, the field is still experiencing a lack of predictive biomarkers and patient selection remains difficult. 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. Cambridge Healthtech Institute’s 2nd Annual Immuno-Oncology Biomarkers & Companion Dx program is designed to bring together clinical immuno-oncologists, researchers from pharmaceutical companies and laboratory medicine leaders to discuss the underlying mechanisms of cancer immunotherapy, its predictive biomarkers as well as existing and emerging clinical assays aiming to improve patient outcomes.

Final Agenda

Monday, March 11

10:30 am Conference Program Registration Open (South Lobby)

INFORMING COMBINATIONS
11

11:50 Chairperson’s Opening Remarks

Paul Robbins, PhD, Senior Director, Immuno-Oncology, Early Development & Translational Oncology, Pfizer, Inc.

12:00 pm KEYNOTE PRESENTATION: Biomarkers to Inform Trial Design and Combinations in Immuno-Oncology

Mazumder_RonRon Mazumder, PhD, MBA, Vice President, Oncology Biomarker Development & Companion Diagnostics, Genentech

I will discuss PD/MOA, predictive and surrogate biomarkers and their use in drug development.


12:30 KEYNOTE PRESENTATION: The Targeted Agent and Profiling Utilization Registry Study: Rationale, Design and Preliminary Findings

Richard SchilskyRichard L. Schilsky, MD, FACP, FSCT, FASCO, Senior Vice President, CMO, American Society of Clinical Oncology

The TAPUR Study, a Phase II, prospective, non-randomized, multi-basket, pragmatic clinical trial aims to identify signals of drug activity when FDA approved drugs are matched to pre-specified genomic targets in patients with advanced cancer. More than 1100 participants have thus far received one of 15 possible treatments. Four study cohorts have closed due to lack of anti-tumor activity and 16 have expanded to the second stage due to promising preliminary results.

1:00 Session Break

Visiopharm_NEW 1:10 Luncheon Presentation I: Multiplex Image Analysis in The Tumor Microenvironment using Artificial Intelligence

Ben Freiberg, Visiopharm

The phenotypes of cells within the tumor microenvironment has been shown to correlate with disease progression and outcome in cancer patients.  Artificial Intelligence, including machine learning and deep learning, provides tools to accurately define these phenotypes to better understand cancer.

Medgenome 1:40 Luncheon Presentation II: TCR Repertoire Predictive Biomarkers for Immunotherapy Research Speaker

Mazumder_RonAnkita Das, PhD, Marketing Manager, MedGenome Inc


2:10 Session Break

2:30 Chairperson’s Remarks

Paul Robbins, PhD, Senior Director, Immuno-Oncology, Early Development & Translational Oncology, Pfizer, Inc.

2:40 Biomarkers in the Context of I/O Combinations

Paul Robbins, PhD, Senior Director, Immuno-Oncology, Early Development & Translational Oncology, Pfizer, Inc.

I/O and non-I/O combinations are achieving unprecedented clinical successes and represent our best opportunity to expand the patient subsets who derive clinically meaningful benefit from treatment. Optimal use of I/O combinations requires detailed knowledge of the mechanisms and interdependencies of tumor biology and immunology underlying the disease and response to therapy. A key question is whether I/O biomarkers in use/development for monotherapy are appropriate for use with I/O and non-I/O combinations.

3:05 Immuno-Oncology Biomarkers: What’s New?

Green_GeorgeGeorge Green, PhD, Head, Pharmacodiagnostics, Bristol-Myers Squibb

Precision medicine continues to transform treatment paradigms through development of new biomarkers and interpretation of clinical data. Testing for Immuno-Oncology biomarkers, such as PD-L1, and emerging ones, such as tumor mutational burden, may help optimize treatment decisions when assessed individually or in combination. The advancement of increasingly complex biomarkers also brings a need for advanced diagnostic tools.  We will discuss biomarkers, their dynamic monitoring, and assessment in the evolving field of pharmacodiagnostics.

GuardantHealth_new

3:30 NEW: Plasma-Based Biomarkers and Immunotherapy Drug Development

Justin Odegaard, MD, PhD, Vice President, Clinical Development, Guardant Health, Inc.

4:00 Genomic Application in Immuno-Oncology

James Yen, PhD, Senior Scientist, Neogenomics

4:15 PANEL DISCUSSION: Enhancing the Impact of Biomarkers in Clinical Trials with I/O Combinations

Moderator: Paul Robbins, PhD, Senior Director, Immuno-Oncology, Early Development & Translational Oncology, Pfizer, Inc.

Panelists: Speakers of the Day

  • Current and emerging biomarkers for patient selection for immuno-oncology therapies – will current assays be combined or completely superseded? Are standard clinical biomarkers being overlooked in I/O trials?
  • Beyond the biopsy - what is the current utility and future potential of blood-based biomarkers?
  • NGS panels have arrived – are we ready to analyze and interpret the data from complex transcript panels? How can biomarker data be used to improve target discovery and/or combo prioritization?
  • Harmonization of multiple assays for the similar biomarker(s) – should this be achieved during development and whose responsibility is it?

4:40 Refreshment Break and Transition to Plenary Session


5:00 Plenary Keynote Session (Room Location: 3 & 7)

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

7:30 Close of Day

Tuesday, March 12

7:30 am Registration Open and Morning Coffee (South Lobby)


8:00 Plenary Keynote Session (Room Location: 3 & 7)

9:15 Refreshment Break in the Exhibit Hall with Poster Viewing

GENOMIC DETERMINANTS OF RESPONSE
11

10:15 Chairperson’s Remarks

Roopa Srinivasan, PhD, Senior Director, Head, Translational Research, Immuno-Oncology & Combinations, GSK

10:25 Genomic Determinants of Response to Pembrolizumab: Impact on Combination Strategies for Cancer Immunotherapy

Terri McClanahanTerri McClanahan, PhD, Executive Director, Molecular Discovery, Translational Medicine, Merck

Pan-cancer molecular biomarkers of immunotherapy response can identify 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, and provide a framework for novel approaches to cancer therapy.

10:55 Biomarker Hypotheses Derivations to Drive Translational Research for IO Agents - Strengths and Challenges

Roopa Srinivasan, PhD, Senior Director, Head, Translational Research, Immuno-Oncology & Combinations, GSK

Biomarkers are critical in projecting pharmacodynamic activity and efficacy signals of various immuno-oncology drugs. The process of evaluation is continuous from bench to bedside and back to ensure that hypotheses projected are valid in clinical trials. Multiple approaches both non-clinical and clinical are necessary to define optimum biomarkers and functions they measure, some of which will be discussed.

11:25 Opportunities and Challenges of Liquid Biopsy IVDs for Cancer Immunotherapy

Destenaves_BenoitBenoit Destenaves, PharmD, Director, Diagnostics Lead, Precision Medicine and Genomics, Innovative Medicines and Early Development (IMED) biotech unit, AstraZeneca

Next Generation Sequencing and Liquid biopsies offer exciting novel opportunities to bring innovative drugs to patients. But these opportunities do not come without challenges and will need to be resolved particularly when looking at genomic signatures such as Tumor Mutational Burden (TMB).

TransHitBiomarkers 11:55 How Biospecimen Sourcing Can Impact Your R&D Results

Vanessa Tumilasci, PhD, Commercial Director, Trans-Hit Bio

Biospecimen sourcing is becoming a challenge for many scientists who need to respect timelines for R&D plans as well as regulatory and ethical constraints. Are the scientists working with the samples aware of all the imperatives to obtain them: quality, respect of laws, ethics and regulations?

12:10 pm Advanced Multiplexing Reagents for Measuring Biomarker Expression and Cell Behavior in Tissue

Phillips_BonnieBonnie Phillips, PhD, Field Application Scientist, Ultivue  

The benefits of multiplex immunohistochemistry assays for tissue analysis are numerous. High-level multiplexing, whole slide imaging, workflow compatibility, and spatial analysis are all must-have requirements for effective multiplex IHC solutions. Ultivue’s InSituPlex® technology addresses each of these needs and enables researchers to unmask the true biology of tissue samples

12:25 Session Break

MolecularMD_tagline 12:35 Luncheon Presentation I :Codevelopment
 of a Drug and a Diagnostic…Controlling the Diagnostic Channel

Snyder_DanDan Snyder, President & CEO, MolecularMD


Discovery-Life-Sciences 1:05 Luncheon Presentation II: Large-Scale Cohort Development Supporting Companion Dx and IO
Biomarker Discovery

Fahl_ShawnShawn Fahl, PhD, Senior Research Scientist, Discovery Life Sciences

This session will provide case studies in custom cohorts designed to expedite biomarker research through the integration of high-quality biosamples with clinical data, phenotypic, and genotypic characterizations. For example, a 200 patient NSCLC cohort including tissue microarray blocks, PD-L1 stains/imaging, and oncogene sequencing data for rapid biomarker analysis.

1:35 Refreshment Break in the Exhibit Hall with Poster Viewing

COMPANION DIAGNOSTICS IN IMMUNO-ONCOLOGY
11

2:05 Chairperson’s Remarks

Kenneth Emancipator, MD, Executive Medical Director and Head of Companion Diagnostics, Merck & Co., Inc.

2:10 Companion Diagnostics in Immuno-Oncology

Donna Roscoe, PhD, Chief, Molecular Genetics Branch, Division of Molecular Genetics and Pathology Devices, Office of In Vitro Diagnostics and Radiological Health, FDA CDRH

This session will focus on the implementation of immuno-oncology diagnostic tests in clinical trials, including understanding the regulatory implications of different approaches, validation of emerging pan-tumor CDx claims, and complementary diagnostics vs. companion diagnostics.

2:40 PD-L1 as a Companion Diagnostic for Tumors beyond Non-Small Cell Lung Cancer: It’s the Same Thing, Only Different

Emancipator_KennethKenneth Emancipator, MD, Executive Medical Director and Head of Companion Diagnostics, Merck & Co., Inc.

The PD-L1 companion diagnostic had a huge impact on the clinical development of pembrolizumab, making it the first immunotherapy approved as a first-line agent for non-small cell lung cancer. However, this is just the beginning of the story, not the end. Adapting the PD-L1 diagnostic to incorporate immune cell expression facilitated approval of pembrolizumab for several additional indications and may shed light on the mechanism of action of checkpoint inhibitors.

3:10 Companion Diagnostics for the Adjuvant Setting for Immune Therapy

Rimm_DavidDavid L. Rimm, MD, PhD, Professor of Pathology and of Medicine (Medical Oncology); Director of Pathology Tissue Services; Director of Translational Pathology, Yale University School of Medicine

Companion diagnostics for immune checkpoint blockade (ICB) therapy have all been designed and executed by the pharma companies producing the drugs. However, in the adjuvant setting, better markers are needed, but unlikely to come from pharma where the companion test is either already established or not required. In the adjuvant setting, since the side effects are toxic and only 1 in 5 benefits, biomarkers that predict which patients do NOT need drug are most important. Most likely these biomarkers will be produced by biotech, since they need to exclude rather than include the ICB drugs. Here we will discuss biomarkers with promise for selection in the adjuvant setting for ICB therapy. They will include both gene expression profiles and multiplex quantitative fluorescent tests with predictive potential.

NeoGenomics3:40 Detecting Immunosuppressive Cells and Their Mechanisms by Multiplex Immunofluorescence

Anna Juncker-Jensen, Scientific Liaison, Senior Scientist, NeoGenomics Laboratories

 

4:10 St. Patrick’s Day Celebration in the Exhibit Hall with Poster Viewing

5:00 Breakout Discussions in the Exhibit Hall

Precision Medicine in IO

George Green, PhD, Head, Pharmacodiagnostics, Bristol-Myers Squibb

  • How can we better identify clinically relevant combination therapies upfront?
  • Are there ways to improve patient selection for IO therapy?
  • What are common challenges with IO therapy in the real-world setting?

Emerging Technologies for IO Biomarkers

Benoit Destenaves, PharmD, Director, Precision Medicine Lead, Precision Medicine and Genomics, Innovative Medicines and Early Development, AstraZeneca

Parallel Analysis of Circulating Biomarkers in Immunotherapy

Genevieve Boland, MD, PhD, Director, Melanoma Surgery Program, Massachusetts General Hospital; Director, Surgical Oncology Research Laboratories, Massachusetts General Hospital; Assistant Professor, Harvard Medical School; Associate Member, Broad Institute

  • Clinical application of blood-based biomarkers in melanoma
  • Unmet clinical needs in blood-based biomarkers
  • Microvesicle applications in immunotherapy

6:00 Close of Day

Wednesday, March 13

7:30 am Registration Open and Morning Coffee (South Lobby)


8:00 Plenary Keynote Session (Room Location: 3 & 7)

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

EVOLUTIONARY BIOMARKERS: COHESIVE STRATEGIES ACROSS ALL STAGES OF DRUG DISCOVERY AND DEVELOPMENT
11

10:50 Chairperson’s Remarks

Jean-Claude Marshall, PhD, Head, Clinical Biomarkers, Early Clinical Development, Pfizer

11:00 Biomarkers in Early Clinical Trials, an Industry Perspective

Marshall_JeanClaudeJean-Claude Marshall, PhD, Head, Clinical Biomarkers, Early Clinical Development, Pfizer

This talk will focus on the implementation and utilization of clinical biomarkers in early clinical development in multiple therapeutic areas. The discovery, development and validation of these assays to a variety of regulatory levels is an increasing challenge against the need for faster and more focused Phase I and II clinical trials.

11:30 Strategies for Integrating Biomarkers into Antibody-Drug Conjugates Development Programs

Onsum_MattMatt Onsum, Director & Head, Diagnostics, Analytics & Biomarkers, Seattle Genetics

The co-development of a predictive biomarker with a targeted therapy has the potential to accelerate development timelines and improve the probability of technical success of the drug candidate. The identification, validation, and clinical application of a predictive biomarker, however, remains challenging. In this talk I will present a framework for predictive biomarker development with an emphasis on applications to antibody-drug conjugate development.

12:00 pm Coding and Coverage Considerations to Broad Based Genomic Profiling in Clinical Laboratories

Sireci_AnthonyAnthony (Nino) Sireci, Medical Director, Diagnostics Lead, Medical Affairs, Loxo Oncology

The development and maturation of precision oncology is expanding the number of targetable biomarkers across both solid and heme tumors. Broad based genomic profiling of tumor tissue which can detect all classes of genomic alterations in a small tissue sample are likely to be the most efficient way to identify patients for targeted therapies while conserving precious tissue. Various coding and coverage realities play a part in the laboratory’s ability to implement such efficient testing over single gene algorithms.

12:30 Enjoy Lunch on Your Own

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

INNOVATION IN PATIENT SELECTION
11

1:50 Chairperson’s Remarks

Theresa LaVallee, PhD, Vice President, Translational Medicine and Regulatory Affairs, Parker Institute for Cancer Immunotherapy

2:00 In silico Analysis of Concomitant Medications in Atezolizumab Trials

Nagarkar_DeeptiDeepti Nagarkar, PhD, Scientific Manager, Cancer Immunology, Research, Genentech

Concomitant medications (ConMeds) are relevant clinical covariates that may influence response to cancer immunotherapy (CIT). Pharmacological action based drug baskets were generated to explore immune modulation in cancer subjects receiving Atezolizumab. We observed changes in inflammatory response genes in diabetic patients receiving single or combination treatments at the start of the trial. This suggests that curation of ConMeds may help stratify immune set point of patients receiving CIT.

Adaptive-Biotechnologies 2:25 Implementing Immunosequencing as New Molecular Biomarkers of Response to Immunotherapy

Catherine Sanders, Senior Director, Research and Business Development, Adaptive Biotechnologies Corp.

Adaptive Biotechnologies’ immunosequencing technology combines bias-controlled multiplex PCR, high-throughput sequencing, and sophisticated bioinformatics. In solid tumors, the immunoSEQ Assay accurately quantifies TIL density and clonality, with preclinical and clinical applications to inform repertoire changes in response to single agent or combination therapies that have potential prognostic and predictive value.

2:40 The Parker Institute’s Collaborative and Integrated Approach to Immuno-Oncology: Innovative Clinical Trials and Biomarkers

LaVallee_TheresaTheresa LaVallee, PhD, Vice President, Translational Medicine and Regulatory Affairs, 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.

3:05 Clinical Predictors of T Cell Fitness for CAR T Cell Manufacturing and Efficacy in Multiple Myeloma Using RShiny, FlowType, Citrus and Spade

Pruteanu_IulianIulian Pruteanu-Malinici, Investigator III, Lab Head, Immuno-Oncology, Novartis

The optimal clinical setting for CAR T cell therapy in multiple myeloma (MM) remains uncertain. In CLL patients treated with anti-CD19 CAR T cells (CART19), frequency of an early memory (early-mem) T cell phenotype (CD27+ CD45RO- CD8+) at time of leukapheresis was predictive of clinical response independently of other patient- or disease-specific parameters and was associated with enhanced capacity for in vitro T cell expansion and CD19-responsive activation (Fraietta et al. Nat Med 2018); T cell fitness is therefore a major determinant of response to CAR T cell therapy. Here, we report that higher frequency of early-mem T cells and CD4/CD8 ratio in the leukapheresis product are associated with favorable clinical response to anti-BCMA CAR T cells (CART-BCMA) in relapsed/refractory MM patients.

3:30 Session Break

PREDICTIVE BIOMARKER ASSAY DEVELOPMENT
11

3:40 Chairperson’s Remarks

Kurt SchalperKurt A. Schalper, MD, PhD, Assistant Professor, Pathology and Medicine (Medical Oncology); Director, Translational Immuno-Oncology Laboratory, Yale Cancer Center


3:45 Deconvoluting Cellular Determinants of Anti-Tumor Immune Recognition

Ash AlizadehAsh Alizadeh, PhD, Associate Professor of Medicine, Divisions of Oncology & Hematology, Stanford University School of Medicine

I will discuss our work on developing techniques to characterize the cellular organization of tumor microenvironments, with a focus on compositional diversity and clinical significance of hematopoietic cell subsets. I will describe the genesis and application of deconvolution algorithms to resolve tumor subpopulations and cell type-specific expression programs from genomic profiles of diverse human tumors. I will discuss the clinical translational potential in the context of individualized approaches to immuno-oncology.

4:15 Development and Validation Considerations for Clinical Laboratory Methods for Mutational Burden Determination

Konnick_EricEric Konnick, MD, MS, Assistant Professor; Associate Director, Genetics and Solid Tumors Laboratory, University of Washington

Recent studies have indicated that increased mutational burden and microsatellite instability may predict response to anti-cancer therapies targeting the immune system. Many pre-analytical, analytical, and design factors may contribute to the ability of a clinical diagnostic test to appropriately measure the biomarker of interest. A thorough understanding of the relevant factors that can impact patient results will allow an appropriate comparison of existing methods and implementation of new assays.

4:45 Selected Poster Presentation: Development and Validation of a Deep Learning Algorithm for PD-L1 Scoring in Tumour Cells and Immune Cells

Vandenberghe_Michel Michel Vandenberghe, PharmD, PhD, Senior Scientist, Precision Medicine Labs, Precision Medicine and Genomics, IMED Biotech Unit, AstraZeneca

Treatment decisions in oncology are commonly informed by the visual assessment of immunohistochemistry (IHC) biomarkers (such as PD-L1 expression) by pathologists. However, pathology services face mounting pressure as diagnostic demand increases and workforce decreases. Digital pathology and artificial intelligence have the potential to streamline the diagnostic workflow thereby improving pathologists' workload, accelerating turn-around-times and facilitating access to testing. Here, we report the in-house development and analytical validation of a deep learning algorithm for automated scoring of PD-L1 expression in samples processed with the VENTANA PD-L1 (SP263) Assay. The algorithm was trained to score PD-L1 expression in tumour cells and in immune cells using 29318 manually annotated cells across a set of 150 PD-L1 IHC images from 30 urothelial carcinoma (UC) samples. The algorithm was then validated in an independent cohort of UC samples. In the validation cohort, the algorithm demonstrated high inter-scan reproducibility (99% overall percent agreement, N=197), high inter-scanner reproducibility (100% overall percent agreement, N=33) and substantial agreement with pathologist-based scoring of PD-L1 expression (84% overall percent agreement, N=195). In conclusion, this study shows that our deep learning algorithm has favourable analytical characteristics to assist pathologists in scoring PD-L1 in both tumour cells and immune cells.

4:55 Selected Poster Presentation: Multiparametric Flow Cytometry Analysis of Checkpoint Inhibitors (PD-1 and PD-L1) in Dissociated Tumor and Normal Tissues

Fahl_Shawn Shawn Fahl, PhD, Senior Research Scientist, Research & Development, Discovery Life Sciences

Immune checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1, have been approved as first or second-line therapies in melanoma, lung cancer, renal cancer, and urothelial cancer. More recently, these therapies have been approved in MSI-high colorectal cancer. In the Discovery Life Sciences clinical network, we observe high percentages of patients on PD-1 and PD-L1 immunotherapies across the relevant indications. However, despite these successes, there are still some patients that have no or partial remission in response to these therapies. Understanding the expression of checkpoint inhibitors within the complex cellular components of the tumor microenvironment provides not only crucial information on the potential functionality of these therapies, but also allows for the identification of potential companion diagnostic markers to stratify patients prior to treatment. We present below our initial exploration of these markers in our dissociated tumor and normal tissues via multiparametric flow cytometry to evaluate their expression on cellular subsets in both cancerous and non-cancerous tissues.

5:05 Selected Poster Presentation: Tumor Mutational Burden (TMB) Analysis Using an Ultra-High Multiplexed 20,000-Amplicon NGS Panel in a Rapid 4-Hour Workflow

Pendleton_Kathryn Kathryn Pendleton, PhD, Scientist, Paragon Genomics, Inc.

Tumor mutational burden (TMB) is currently gaining significant importance in the field of immuno-oncology due to its correlation with patient response to checkpoint inhibitor chemotherapy. Traditionally, TMB is calculated using whole exome sequencing via laborious hybrid-capture based methods. However, targeted sequencing approaches provide better coverage of the genetic regions of interest at lower costs. Here we present an ultrafast, 4-hour method for preparing target enriched NGS libraries for assessing TMB - the CleanPlex® technology. This method would streamline and lower the cost of immuno-oncology studies. This is a multiplex-PCR-based technology, that provides a highly efficient, accurate and robust method for unbiased enrichment of tens of thousands of target regions while minimizing non-specific primer-primer interactions and GC bias and maximizing coverage uniformity.

5:15 Close of Conference Program

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