Cambridge Healthtech Institute’s Eighth Annual

Clinical and Translational Biomarkers

June 11-12, 2018 | Westin Boston Waterfront | Boston, MA



The promise of personalized medicine has been driven by the need to accurately predict patient response to therapy while ensuring drug efficacy and safety. Reducing costs and the time required for drug development is also a driving force in the use of biomarkers. Cambridge Healthtech Institute’s Eighth Annual Clinical and Translational Biomarkers meeting will cover novel biomarker discovery, clinical and analytical biomarker validation, and the role of biomarkers in clinical decision-making.

Final Agenda

Sunday, June 10

4:30-6:30 pm Short Course and Conference Registration

5:00-8:30 Dinner Short Course*

SC1: Fit-for-Purpose Biomarker Assay Development and Validation

*Separate registration required

Monday, June 11

7:00 am Conference Registration and Morning Coffee

8:00 Organizer’s Welcome

 

OPENING PLENARY SESSION: EMERGING APPROACHES FOR CANCER

8:05 Chairperson’s Opening Remarks

George A. Green, IV, PhD, Head, Pharmacodiagnostics, Bristol-Myers Squibb

8:10 Clinical Genomic Profiling Using the MSK-IMPACT™ Large Panel NGS Assay to Guide Patient Selection for Targeted and Immune Therapies

Marc Ladanyi, MD, William J. Ruane Chair in Molecular Oncology, Molecular Diagnostics Service and Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center

As the centerpiece of an institutional initiative in clinical cancer genomics, we have implemented large scale genomic profiling for targetable cancer drivers and other cancer-relevant alterations in all patients with advanced solid cancers. Since 2014, over 23,000 patients have been profiled using the MSK-IMPACT™ targeted large panel, capture-based DNAseq assay. MSK-IMPACT™, which received FDA clearance in 2017, allows robust detection of somatic mutations in all known cancer genes, copy number changes and select cancer fusion gene rearrangements, as well as assessing overall tumor mutation burden and microsatellite instability. Patients are also screened for oncogenic fusions by targeted RNAseq and for germline cancer predisposition alleles and evidence of clonal hematopoiesis.

8:40 Widgets to Cancer Patient-Specific Digits: The Case for Out-of-Clinic Objective Measures and Their Potential Impact to Remote Patient Monitoring in Precision Oncology and Discovery

Christopher M. Hartshorn, PhD, Program Director, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health

Albeit the case for long-term, out-of-clinic monitoring has been obvious for many chronic diseases, the case for cancer has not been as clear. The National Cancer Institute has begun piloting and funding various aspects to enable an Internet of Cancer Medical Things. This talk will focus on these efforts currently and prospectively as well as the overall vision to coordinate a much broader initiative to improve our understanding of cancer progression and improve the delivery of cancer care.

9:10 Coffee Break in the Exhibit Hall with Poster Viewing

 

BIOMARKER-DRIVEN CLINICAL TRIALS

9:55 Chairperson’s Remarks

Robert A. Beckman, MD, Professor, Oncology, Biostatistics, Bioinformatics, and Biomathematics, Lombardi Comprehensive Cancer Center and Innovation Center for Biomedical Informatics, Georgetown University Medical Center

10:00 Clinical Monitoring of Biomarkers to Guide Informed Treatment

Brittany Bahamon, Scientist I, Translation & Biomarker Research, Takeda Pharmaceuticals, Inc.

De novo and acquired resistance mechanisms remain a persistent problem to long-term treatment benefit. To understand the molecular and biological mechanisms underlying the response and resistance to the mTOR inhibitor, TAK-228, a variety of human specimens collected at baseline, during treatment and at progression were analyzed with diverse approaches such as immunochemistry, sequencing or circulating tumor cell numeration. In a clinical trial testing the combination of hormonal therapy with TAK-228 in patients with advanced or metastatic estrogen receptor positive breast cancer, sequencing of plasma ctDNA at baseline uncovered mutations typical from repeated exposure to hormonal therapies. At treatment relapse, drastic increase in mutation and molecular alterations in a subset of patients suggested novel acquired escape mechanisms, possibly linked to impaired genome integrity surveillance that would support the rational use of immuno-therapy. Continuous monitoring of biomarkers in clinical practice should warrant better treatment options for cancer patients.

10:30 Novel Adaptive Design for a Confirmatory Basket Trial and Best Practices for Application

Robert A. Beckman, MD, Professor, Oncology, Biostatistics, Bioinformatics, and Biomathematics, Lombardi Comprehensive Cancer Center and Innovation Center for Biomedical Informatics, Georgetown University Medical Center

Increasingly, tumors are defined based on molecular subtypes, which if shared across histologies, may be pooled into basket trials, facilitating development of agents targeted at small molecular subgroups. To date, basket trials have been used either for exploratory early development, or for confirmation only in cases where a transformational benefit is anticipated. This presentation discusses a confirmatory basket trial design that is generally applicable to all beneficial therapies.

11:00 Illuminating Biology

Mark Bobrow, Senior Director, Research, 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.

11:30 The Application of a Novel Biomarker of Cell Division and Disruption in Drug Discovery and Development

Martin Shaw, Business Development Manager, AroCell AB

AroCell TK210 ELISA is a novel, sensitive and specific assay for serum Thymidine Kinase 1, a well-known biomarker of cell division and disruption. Data will be presented on its application to in vitro drug discovery and clinical studies. Data will be presented on both solid and hematological malignancies.

Excelra11:45 Role of Biomarkers in Drug Development and Clinical Practice for the Treatment and Management of NSCLC

Michael Liebman, PhD, Scientific Advisor, Excelra Knowledge Solutions

Clinical research should address the entire disease process of NSCLC, from risk, through diagnosis to treatment and outcome. The true value of a biomarker database should be measured by the critical questions that it can address for the success of the clinical trials and accelerating drug development.


12:00 pm Luncheon Presentation: Ultra-Sensitive Detection of Proteomic and Genomic Immuno-Oncology Biomarkers Using SIMOA (Single Molecule Array)

Dan Sikkema, Vice President, Accelerator Services, Quanterix

Advances in immuno-oncology in recent years have benefited from the appropriate selection of biomarkers for diagnosis and predicting treatment benefit, as well as monitoring efficacy and safety post-treatment. Use of readily available specimen types such as serum or saliva will permit more frequent and cost-effective monitoring of health status. The ability to measure low-frequency proteins combined with direct detection of genomic (ctDNA, microRNA) material with a single technology will provide new advancements to the field.

LIQUID BIOPSY FOR PRECISION MEDICINE

1:25 Chairperson’s Remarks

Carolyn Compton, MD, PhD, Professor, Life Science, Arizona State University; CMO, ASU Complex Adaptive Systems Institute; CMO, National Biomarker Development Alliance

1:30 Development of Next-Generation Sequencing Assays for Oncology Translational and Clinical Research

Ambar Ahmed, Senior Scientific Manager, Oncology Translational Sciences, AstraZeneca

Recent studies report discordance in somatic variants between tissue and plasma from the same patient. We designed a replicate study using clinical plasma samples analyzed through four commercial NGS vendors to examine factors contributing to discordance, including biological and technical aspects. Substantial variability in variant calling among the ctDNA assays was observed and comparison of results to tumor sequencing revealed a range of sensitivity (41-94%) and positive predictive value (33-89%).

2:00 Transforming Immuno-Oncology with ctRNA and ctDNA Liquid Biopsy Solutions

Shidong Jia, MD, PhD, Professor, Harbin Medical University; Founder & CEO, Predicine, Inc.

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 and clinical application of circulating RNA- and DNA-based liquid biopsy tests, including at 51-gene Predicine DDR panel for DNA damage repair, a 180-gene PredicinePLUS panel for common cancer variants, and a 600-gene PredicineATLAS panel for tumor mutation burden (TMB). Case studies will be presented for inhibitors of PD-1/PD-L1, PARP, AR in support of personalized cancer care and precision clinical trials.

2:30 Extracellular Vesicles and Platelets: A Strong Friendship in CancerLand Detection
Bakhos A. Tannous, PhD, Associate Professor, Neurology, Harvard Medical School; Director, Experimental Therapeutics and Molecular Imaging Lab; Director, Interdepartmental Neuroscience Center; Director, MGH Viral Vector Development Facility, Massachusetts General Hospital

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

4:10 Chairperson’s Remarks

Carolyn Compton, MD, PhD, Professor, Life Science, Arizona State University

4:15 Liquid Biopsies in Precision Medicine in Cancer

Filip Janku, MD, PhD, Associate Professor, Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center

Molecular testing of liquid biopsies utilizing plasma cell-free DNA is a promising tool for minimally invasive molecular diagnostics and monitoring. As tumor DNA comprises a small fraction of total cell-free DNA, highly sensitive and accurate techniques are required for cancer mutation detection. PCR-based technologies can detect a low frequency of molecular aberrations in cfDNA, but these approaches cannot sample many target sites. NGS can cover a variety of targets, but at higher cost and possibly lower sensitivity.

4:45 Preanalytical Variables and the Liquid Biopsy: The CAP, ASCO and the Moonshot BloodPAC Assess the Need for Standards

Carolyn Compton, MD, PhD, Professor, Life Science, Arizona State University; CMO, ASU Complex Adaptive Systems Institute; CMO, National Biomarker Development Alliance

The Beau Biden Moonshot Blood Profiling Atlas in Cancer (BloodPAC) group consisting of industry and academic partners has published their recommendations for core data elements that are essential for genomic databases built on liquid biopsy assays, including essential preanalytical factors. These have been reviewed by the FDA with the objective of facilitating product development in the future. The widespread adoption of the guidelines of these two authoritative groups would help to ensure the necessary molecular quality and consistency of liquid biopsy analysis results and reduce the problem of employing blood specimens of unknown provenance in clinical studies and clinical application.

5:45 Welcome Reception in the Exhibit Hall with Poster Viewing

Tuesday, June 12

7:25 am Interactive Breakout Discussion Groups with Continental Breakfast

 

LIQUID BIOPSY FOR IMMUNO-ONCOLOGY

8:25 Chairperson’s Remarks

Theresa L. Whiteside, PhD, Professor, Pathology, Immunology and Otolaryngology, University of Pittsburgh Cancer Institute

8:30 Tumor-Derived Exosomes as Potential Biomarkers of Cancer Progression and Immune Dysfunction in Cancer

Theresa L. Whiteside, PhD, Professor, Pathology, Immunology and Otolaryngology, University of Pittsburgh Cancer Institute

Plasma-derived exosomes are emerging as promising non-invasive correlates of cancer progression. In patients with solid tumors or hematological malignancies, plasma exosomes carry a cargo enriched in immunosuppressive proteins. As immune suppression is one of the hallmarks of cancer progression, circulating exosomes rich in inhibitory molecules are implicated in mediating systemic immune suppression.

9:00 Profiling the Tumor Immune Microenvironment by Means of Liquid Biopsy

Samir Hanash MD, PhD, Director, McCombs Institute for Cancer Early Detection and Treatment, MD Anderson Cancer Center

Interest in liquid biopsy has largely focused on ctDNA. However, plasma has a rich content in cells, extra-cellular vesicles and biomolecules that inform about tumor features, the microenvironment and the status of the immune response. Progress in defining the tumor microenvironment in solid tumors by means of liquid biopsy will be presented.

9:30 Clinical Applications of cfDNA for Targeted and Immune Therapies

Rebecca Leary, PhD, Lab Head, Next Generation Diagnostics, Novartis Institutes for BioMedical Research

Circulating tumor DNA (ctDNA) provides an opportunity for non-invasive assessment of tumor genotype, and may enable rational use of targeted and/or immune modulating therapies at several clinical milestones. Implementation of ctDNA-based assays across clinical and research settings highlights important assay characteristics and suggests future clinical applications.

10:00 Molecular Analysis of an Adaptive T Cell Response against an IL-12 Adjuvanted Vaccine: From Molecule to Mechanism

Wyatt McDonnell, Graduate Fellow, Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine

The cytokine IL-12 is known to enhance the function and quality of cytotoxic T lymphocytes (CTLs) against antigens, especially in the context of vaccines. In this study, we analyzed samples from the HIV Vaccine Trial Network (HVTN) study 087. We report the enhancement of the cellular response in individuals receiving IL-12 and identify several potential markers of successful IL-12 adjuvanted vaccination.

10:30 Coffee Break in the Exhibit Hall with Poster Viewing

 

ASSAY DEVELOPMENT AND CLINICAL IMPLEMENTATION FOR GENOMIC TESTS

11:10 Chairperson’s Remarks

Rajyalakshmi (Raja) Luthra, PhD, Director, Molecular Diagnostics Laboratory; Director, Molecular Genetics Pathology Fellowship Program; Professor, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center

11:15 Integration of Circulating Cell-Free DNA (cfDNA) Mutation Testing into Precision Medicine Paradigm

Rajyalakshmi (Raja) Luthra, PhD, Director, Molecular Diagnostics Laboratory; Director, Molecular Genetics Pathology Fellowship Program; Professor, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center

Mutation analysis of circulating cell-free DNA (cfDNA) from plasma is slowly being integrated into cancer patient management as a minimally invasive alternative to tissue based genotyping. However, implementation of cfDNA testing for patient care is faced with several pre-analytical and analytical challenges. This talk addresses potential role and limitations of cfDNA mutation testing using NGS and digital PCR platforms in a molecular diagnostic laboratory for cancer patient management.

11:45 Technical Aspects of NGS Assays for Oncology Translational and Clinical Research

Daniel Stetson, PhD, Associate Principal Scientist, AstraZeneca

The increased acceptance of liquid biopsies for precision medicine demonstrates a critical need for a sensitive and specific assay platform. Next Generation Sequencing (NGS) has the capability of detecting multiple types of genetic aberrations and can be used with many sample types including ctDNA. The technical aspects of improving sensitivity and specificity of NGS assays will be discussed including library preparation from cfDNA, unique molecular barcoding, and comprehensive variant calling.

12:15 pm Precision Oncology: Practical Strategies for Genomic Test Implementation with Case Vignettes

Christina Lockwood, PhD, Associate Professor, Director, Genetics and Solid Tumors Laboratory, University of Washington

Next-generation sequencing is a valuable tool for generating patient-specific genetic information for clinical diagnostics and optimal therapy selection. The heterogeneous somatic mutational landscape in cancer makes NGS particularly appealing due to the ability to accurately and simultaneously detect multiple mutations across many genes, even if present in a minority of cells. The complexity of NGS assays necessitates unique quality control and validation considerations that integrate informatics and variant interpretation.

12:45 Close of Conference