Companion Diagnostics and Clinical Biomarkers

2019 Archived Content

Clinical biomarkers and companion diagnostics play pivotal roles in clinical development and market access of new therapeutics as well as deliver significant patient benefits, healthcare cost savings, and revenue opportunities. Population genetics and pharmacogenomics became platforms for new drug discovery with NGS enabling sophisticated approaches for target and pathway identification and validation. Pharmaceutical companies are embracing biomarkers as a way to decrease drug failures in the clinic by streamlining patient selection and stratification. These current trends emphasize the need for open discussion between pharma and diagnostics partners to find common ground, address strategy and technology issues, and form strong mutually beneficial and sustainable partnerships. Cambridge Healthtech Institute’s Companion Diagnostics and Clinical Biomarkers program is designed to bring together major stakeholders in the field of drug diagnostics co-development to foster the science and business strategies that allow to succeed in rapidly changing healthcare environment.

Final Agenda

Monday, March 11

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

11:50 Chairperson’s Opening Remarks

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

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

Mazumder_Ron Ron 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 The Targeted Agent and Profiling Utilization Registry Study: Rationale, Design and Preliminary Findings

Schilsky_Richard Richard 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

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

Freiberg_Ben 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.

1:40 Luncheon Presentation II: TCR Repertoire as a Biomarker for Immunotherapy Research

Das_Ankita Ankita Das, PhD, Marketing Manager, MedGenome Inc

2:10 Session Break

2:30 Chairperson’s Remarks

Hakan Sakul, PhD, Vice President and Head of Diagnostics, Pfizer

2:40 Global Commercial and Partnership Considerations for Companion Diagnostics

Ferrara_Joseph Joseph V. Ferrara, CEO & President, Boston Healthcare Associates

Key commercialization considerations for drug and test innovators, including balancing test access and quality, and embedding CDx global commercial considerations in pharma and diagnostic company partnerships will be highlighted.

3:10 PANEL DISCUSSION: Novel Approaches to Deal-Making in Companion Dx

The last several years have seen a substantial increase in the number of pharma/diagnostics company deals in development of companion diagnostics. This is in part due to the emerging science generating robust diagnostics biomarkers, providing substrate to develop precision medicines aimed at smaller patient populations. As the dealmaking space continues to be very active, it is the right time to explore new business models to enable efficient co-development of drugs and diagnostics. This panel will focus on the following:

Lessons learned from current model of pharma-diagnostics partnerships
Challenges that pharma and diagnostics companies have run into in these partnerships
New partnership models that could implement solutions to challenges faced and lessons learned
Global commercialization of drug and diagnostics test combinations

Moderator:
Hakan Sakul, PhD, Vice President and Head of Diagnostics, Pfizer

Panelists:

Goswami Joydeep Joydeep Goswami, PhD, President, Clinical Next Gen Sequencing and Oncology Division (CSD), Life SciencesSolutions, Thermo Fisher Scientific

Beard_Andrew Andrew J. Beard, PhD, Head, Business Development & Partnering, Siemens Healthcare Laboratory

Schott_Cecilia Cecilia Schott, PharmD, MBA, Former Vice President, Precision Medicine, Global Product & Portfolio Strategy, AstraZeneca

Febbo_Phillip Phil Febbo, MD, CMO, Senior Vice President, Clinical Genomics, Illumina

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

10:15 Chairperson’s Remarks

Cecilia Schott, PharmD, MBA, Former Vice President, Precision Medicine, Global Product & Portfolio Strategy, AstraZeneca

10:25 Progress toward Personalized Medicine and Prediction of Response in Autoimmune Disease

Mark Curran, PhD, Vice President, Immunology, Head, Companion Diagnostics, Janssen R&D LLC

Rheumatoid Arthritis and Inflammatory Bowel Disease are severe immune diseases. Despite advances in treatment there remains a significant unmet clinical need for new therapies and integrated treatment solutions. We are focused on transforming treatment of autoimmune diseases by applying precision medicine approaches and developing companion diagnostics to achieve higher response rates, deeper remission, interception and eventually prevention of these diseases. Progress and learning toward these objectives will be discussed.

10:55 Validation Tips and Strategies to Receive FDA Authorization for NGS Assays

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 presentation will discuss the regulatory path to successful FDA approval of oncopanels for companion diagnostics and tumor profiling claims, including validation strategies for pan tumor claims. Strategies for validating evolving spectrum of tests using ct/cfDNA will also be discussed.

11:25 Regulatory Landscape for Precision Medicine

Abbott_Brian Brian Abbott, Global Regulatory Lead, CDx Advisor, Amgen

FDA’s Oncology Center of Excellence appears to be running on all cylinders – demonstrating the benefit of this joined approach through coordinated reviews, joint meetings with sponsors and timely and innovative approvals. This presentation will provide a current view of the approvals in the precision medicine space.

11:55 Ultra-Sensitive Biomarker Measurement in Immunotherapy Research Using Simoa Platforms

Warner_Greg_CBM Greg Warner, PhD, Senior Field Applications Scientist, Quanterix Corporation

We will describe the use of the Simoa technology platforms to measure low abundant, yet important, proteins that are emerging as biomarkers for the effectiveness of immuno-oncology therapies. Multiplex measurement of cytokines and other markers of T-cell activation as a response to immunotherapy treatment using these platforms will be highlighted.

12:10 pm Optimizing TMB Use in Cancer Research and Care: The Friends of Cancer Research TMB Harmonization Effort

Mark Stewart, PhD, Vice President, Science Policy, Friends of Cancer Research

Harmonization of methods to quantify TMB will facilitate robust biomarker development and optimize clinical utilization and treatment decision-making. Friends aims to better understand the impact of assay variation on clinical outcomes, align standards, and define best practices for TMB assessment.

12:25 Enjoy Lunch on Your Own

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

2:05 Chairperson’s Remarks

Cecilia Schott, PharmD, MBA, Former Vice President, Precision Medicine, Global Product & Portfolio Strategy, AstraZeneca

2:10 The Importance of Facilitating High Quality Companion Diagnostic Testing for Patients Around the Globe upon Co-Approval of a Drug and a Device

Dennis_Eslie Eslie Dennis, MD, Vice President and Head of Global Medical Affairs, Roche Tissue Diagnostics

Launching a companion diagnostic globally requires a strong, aligned strategic partnership between pharma and diagnostic companies. This aligned strategy is further amplified when the respective Medical Affairs teams collaborate, demonstrating the increasingly important role of Medical Affairs to faciliate successful launches. This presentation will provide a high-level overview on developing a collaborative global Medical co- launch strategy. A broad range of activities preceding and following co-approval enabling patients globally to have access to high quality diagnostic testing will be discussed with representative examples highlighting our experience.

2:40 Integrating China in Global Clinical Trials with a Companion Diagnostic: Challenges and Opportunities

Mata_Marielena Marielena Mata, PhD, Director and Diagnostic Lead, Companion Diagnosticas, Pfizer

The health challenges of China offer big opportunities for multinational pharma companies. Cases of chronic diseases are on the rise in the region, as are lung, gastric, and liver cancers. China alone is likely to be the world’s third-largest pharmaceutical market with sales of more than $50 billion. While the unmet need for oncology drugs in the China market represents a large opportunity, conducting the clinical trials needed for registration presents a number of challenges. Changing regulations, restrictions for the exportation of samples, IP requirements and availability of CROs represent a few of the obstacles that need to be overcome to successfully conduct global registration studies in China. In this talk, we will discuss in more depth these challenges and potential solutions.

3:10 NEW: Streamlined CDx™ - A Proven Strategy to Accelerate Drug Approvals

Mazumder_Ron Jason Gerhold, Global Director, Regulatory Affairs and Quality Assurance, Invivoscribe

Companion Diagnostics have revolutionized precision medicine as they play a pivotal role in defining the efficacy of targeted therapies. Invivoscribe’s Streamlined CDx™ program has been shown to collapse development timelines, improve and accelerate selection of patient cohorts, leading to earlier submissions and accelerated FDA, EMA and PMDA approvals of new targeted therapies. Streamlined CDx™ partnership model has proven successful in approval of the first ever AML companion diagnostic – The LeukoStrat® CDx FLT3 Mutation Assay.

3:40 PANEL DISCUSSION: Driving Innovation through Global Precision Medicine Implementation

This panel will discuss the global implementation of precision medicine across therapeutic areas through multi-disciplinary teams. Advances in technology are moving from lab to the clinic, driving the implementation of new approaches for disease treatment. The regulatory landscape is evolving at a fast pace enabling patients access to targeted therapies. The panel debate will include:

Clinical trial design and regulatory considerations: thinking ahead
What does it take for patients to access new testing modalities thus new therapies?
The ever-growing importance and impact of real-world evidence in clinical practice and regulatory environment

Moderator: Cecilia Schott, PharmD, MBA, Former Vice President, Precision Medicine, Global Product & Portfolio Strategy, AstraZeneca

Panelists: Speakers of the Day

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

5:00 Breakout Discussions in the Exhibit Hall

Around the Globe Strategies for Diagnostics and Clinical Biomarkers

Marielena Mata, PhD, Director and Diagnostic Lead, Companion Diagnostics, Pfizer

Mark Curran, PhD, Vice President, Immunology, Head, Companion Diagnostics, Janssen R&D LLC

Preparing for the implementation of the new EU regulatory framework for CDx
Challenges with single site PMAs and worldwide implementation
Similarities and differences in regulatory requirements across the world. How to plan Dx global strategy and satisfy all requirements

Evolutionary Biomarkers: New Ways to Work with Pharma Companies

Alex Vadas, PhD, L.E.K. Consulting

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

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_JeanClaude Jean-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_Matt Matt 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_Anthony Anthony (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

1:50 Chairperson’s Remarks

Alex Vadas, PhD, L.E.K. Consulting

2:00 SESSION PANEL: What Should be the FDA’s Role in Oversight of LDTs? A Town Hall Discussion

There are multiple ways in which the industry strives for quality including FDA, CLIA and CAP accreditations, clinical quality controls, and laboratory medicine training programs. The purpose of these approaches is to limit risk from bad actors and poor laboratory medicine and are necessary. However diagnostics innovation is evolving at rapid pace and there are (and will continue to be) a number of areas where oversight mechanisms fall short, these may include:

Tests with evolutionary content and interpretation (e.g., BRCA, F1CDx, opioid monitoring)
Personalized tests that are designed uniquely for each patient (e.g., Signatera)

TriConference has assembled a panel of experts coming from different industry vantage points which gives us a unique opportunity to discuss the role of oversight, situations where current approaches fall short, and potential solutions to address deficiencies going forward. The topics to be discussed include:

What is the purpose of oversight in diagnostics?
What mechanisms are in place to ensure quality?
What are ongoing legislative or other changes that may impact laboratory oversight?
What is the role of LDTs (e.g., fill a gap, address deficiencies with FDA-approved tests)?
What are situations where existing regulatory or oversight approaches fall short (panel to identify specific examples and highlight key issues)? For example:
What are real-world issues that may arise from these shortfalls? How do they impact various stakeholders?
Picking two specific examples of evolutionary content and personalized tests what is the path forward?
What are insights for diagnostics companies? What about pharma?

Moderator:
Alex Vadas, PhD, L.E.K. Consulting

Participants:

Putcha_Girish Girish Putcha, MD, PhD, CMO & Clinical Laboratory Director, Freenome

Gutierrez_Alberto Alberto Gutierrez, PhD, Partner, NDA Partners LLC; Former Director, Office of In Vitro Diagnostics and Radiological Health, FDA

Abbott_Brian Brian Abbott, Global Regulatory Lead, CDx Advisor, Amgen

Pratt_Vicky Victoria Pratt, PhD, FACMG, Director, Pharmacogenomics and Molecular Genetics Laboratories, Medical and Molecular Genetics, Indiana University School of Medicine; President, AMP

Dietzen_Dennis Dennis Dietzen, PhD, Associate Professor of Pediatrics and Pathology, Washington University

Moshkevich_Solomon Solomon Moshkevich, General Manager, Oncology & Transplant Businesses, Natera

3:30 Session Break

3:40 Chairperson’s Remarks

Kurt Schalper Kurt 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 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

eric-konnick Eric 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

March 11-12, 2025

March 12-13, 2025