Cambridge Healthtech Institute 제3회

Immuno-Oncology Biomarkers 1: Predictive Biomarkers and Companion Diagnostics

(암면역 바이오마커 1 : 예측 바이오마커와 동반진단)


2018년 6월 11-12일 | Westin Boston Waterfront | 매사추세츠주 보스턴

제약회사 및 바이오테크놀러지 기업이 새로운 면역치료제의 개발 촉진을 목적으로 한 프로그램에 대한 투자를 확대하는 가운데 암면역과 관련성 있는 바이오마커의 발견, 검증에 대한 필요성이 강하게 인식되고 있습니다. 예측 바이오마커와 동반진단을 테마로 한 이 컨퍼런스 프로그램에서는 제약회사 및 대학에서 바이오마커를 연구하고 있는 전문가가 한자리에 모여 암면역에 관계된 예측 바이오마커 및 예후 바이오마커의 개발을 가속시키기 위한 방안, 임상시험에서 이 바이오마커의 유용성, 동반진단으로서의 가능성 등의 토픽에 대해 논의합니다.

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

 

개회 전체 세션:암치료의 새로운 접근

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

 

암 면역치료에서의 환자 선정을 위한 바이오마커와 동반진단

9:55 Chairperson's Remarks

Shirin Khambata Ford, PhD, Global Head, Biomarkers and Diagnostics, Executive Director, Oncology Global Medical Affairs, Merck

10:00 Patient Selection Strategies for Making Precision Medicine a Reality for Immuno-Oncology

Shirin Khambata Ford, PhD, Global Head, Biomarkers and Diagnostics, Executive Director, Oncology Global Medical Affairs, Merck

This talk will highlight the development and implementation of the PD-L1 IHC testing globally to select patients for pembrolizumab treatment across different tumor types. It will also focus on some of the more recent biomarker approaches that are being utilized to optimally select patients who will benefit from anti-PD1 therapies such as microsatellite instability/mismatch repair deficiency assessment and tumor mutation burden.

10:30 Transitioning from Exploratory Tumor Mutation Burden Assays to IVD Platforms for Immuno-Oncology

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

A range of methods exist for measuring tumor mutation burden (TMB), including whole exome sequencing (WES) and genomic profiling assays (e.g. FoundationOne®). While WES is used in research, more efficient methods, such as FoundationOne®, are being assessed for clinical use. Therefore, harmonization of various tests will be essential to establish diagnostics. This discussion will expand on previous data demonstrating concordance between WES and FoundationOne® in pursuit of an IVD assessing TMB.

11:00 Differential Response of Target Germline Variation Reveals Patient Enrichment Strategy for a Novel Cancer Immunotherapy

Xingfeng Bao, PhD, Director, Immuno-Oncology, Eisai

In the discovery and development of cancer immunotherapy, the polymorphic nature of immune therapeutic targets and limited translatability of mouse models make prediction of human response to an immunotherapy challenging. In this presentation, we will discuss an application of human germline genetics and primary human tumor tissues for the characterization and translational biomarker discovery of a novel drug candidate.

11:30 Presentation to be Announced



12:00 pm Luncheon Presentation: Validation of an RNA-Based Immune Profiling Assay for Limiting & Diverse Patient Samples

Natalie LaFranzo, Director, Scientific Projects and Market Development, Cofactor Genomics

The success of immunotherapy development relies on robust approaches for characterizing and interpreting a patient's immune system; specifically, the microenvironment surrounding a tumor. Using RNA-seq and machine-learning informatics, Cofactor's Paragon assay overcomes current challenges associated with commonly used methods, even for limiting and degraded samples. Complex molecular signals are measured and reported in an easy to interpret report. Case study data with control samples and patient materials will be discussed.

면역치료에 대한 반응을 예측하기 위한 바이오마커

1:25 Chairperson's Remarks

David L. Rimm, MD, PhD, Professor, Pathology, Yale University

1:30 Immunophenotyping to Differentiate Responder and Non-Responder Patients in Cancer Immunotherapy

George Poste, DVM, PhD, Chief Scientist, Complex Adaptive Systems, Regents' Professor and Del E. Webb Chair in Health Innovation, Arizona State University

The clinical benefits of immune checkpoint inhibitors in a variety of malignancies are unprecedented. Unfortunately, the level of positive therapeutic response is not consistent across different tumor classes and even in responsive tumor lineages non-responders still dominate. The need for comprehensive immunophenotyping to identify the mechanisms underlying these differential responses and better predict responder patients is an urgent clinical and economic imperative.

2:00 Dual Biomarker Strategy to Understand Novel Translational Biomarkers to Stratify Patients Effectively for Personalized Cancer Immunotherapy

Jianda Yuan, MD, PhD, Senior Director, Translational Oncology, Early Clinical Oncology Development, Merck Research Labs

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. High throughput next-generation sequencing technologies enable us to explore the mechanisms of responses as well as resistance. Emerging dual biomarkers (tumor mutational burden and gene expression profile) allow us to understand novel translational biomarkers to stratify patients effectively for personalized cancer immunotherapy.

2:30 Predicting Response to Immunotherapy: PD-L1 and Beyond

David L. Rimm, MD, PhD, Professor, Pathology, Yale University

Prediction of response to PD-1 axis drugs began with simple IHC-based assessment of PD-L1 with different assays matched to different drugs. More recently, assessment of DNA MMR has gained its first approval as a predictive assay. This presentation will discuss these tests and future more sophisticated tests for protein, including expression in the microenvironment and the tumor, mRNA, as expression signatures, and DNA, including tumor mutational burden.

3:00 Presentation to be Announced

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

4:10 Chairperson's Remarks

David L. Rimm, MD, PhD, Professor, Pathology, Yale University

4:15 The New Precision Medicine: The Role of Dynamic Tumor and Immune Sampling in Immunotherapy

Morganna Freeman, DO, Medical Oncologist, Immunotherapeutics, The Angeles Clinic and Research Institute

4:45 The Genomic and Immunologic Determinants of Response to Cancer Immunotherapy

Rajarsi Mandal, MD, Head and Neck Surgical Oncology Fellow, Memorial Sloan Kettering Cancer Center

Immune checkpoint blockade is a promising approach for the treatment of human malignancies and has led to improved response rates and durable clinical benefit in a subset of patients. However, the extent to which patients derive benefit is diverse and the determinants of response to therapy are ill-defined. We have sought to define the genomic and immunologic determinants of response to immune checkpoint blockade therapies such as anti-CTLA-4 and anti-PD-1. Our work has shown that tumor mutational burden, clonality, and the tumor immune landscape help dictate clinical response to immune-based therapies.

5:15 Tumor Microenvironment as Biomarker for Immunotherapy

Shu-Jen Chen, PhD, CSO, ACT Genomics

The success of immune checkpoint inhibitors in a subset of cancer patients has led to major efforts in identifying predictive biomarkers. In addition to PD-L1 staining and tumor mutational burden, factors such as immune cell compositions and checkpoint molecule profiles, antigen presenting machinery and immune resistance signals, should also be considered when evaluating a patient for immunotherapy. In this talk, a novel chip-based assay to monitor tumor microenvironment using FFPE tissue will be presented.

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

Tuesday, June 12

7:25 am Interactive Breakout Discussion Groups with Continental Breakfast

This session features discussion groups that are led by a moderator who ensures focused conversations around the key issues listed. Attendees choose to join a specific group, and the small, informal setting facilitates sharing of ideas and active networking. Details on the topics and moderators are available on the conference website.

암 면역치료용 액체생검

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 Presentation to be Announced

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

 

바이오마커 및 표적으로서의 종양 신항원

11:10 Chairperson's Remarks

Fred Ramsdell, PhD, Vice President, Research, Parker Institute for Cancer Immunotherapy

11:15 Neoantigens and Their Relationship to Mutational Load, Mismatch Repair and Immune Checkpoint Expression

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

The objectives of this presentation are 1) to review the biological background by which somatic mutations can lead to the generation of private, highly immunogenic tumor antigens (neoantigens), 2) discuss association of neoantigens with mutational burden, mismatch repair and immune checkpoint expression, and 3) to provide an outlook on clinical applications involving assessment of neoantigens and mutational load with regards to response to immune-checkpoint blockade in solid tumors.

11:45 Tumor Neoantigen Selection Alliance (TESLA): Towards Personalized Cancer Vaccines

Fred Ramsdell, PhD, Vice President, Research, Parker Institute for Cancer Immunotherapy

It is now accepted that mutation-derived neoantigens can elicit a tumor-specific immune response. Identifying neoantigens accurately from the exome sequence is a key parameter for the development of such responses and remains a significant variable of the overall process. TESLA is a consortium-based approach involving over 30 groups to identify key parameters in neoantigen prediction. An update on the progress of the program will be discussed.

12:15 pm Driving CD8+ T Cell Responses to Mutational Neoantigens in Tumors - Harnessing Immunogenic Viral Vectors in Combination with Immune Checkpoint Modulators

Karin Jooss, PhD, CSO, Gritstone Oncology

DNA damage may cause mutations in tumors that can generate new antigens, known as tumor-specific neo-antigens (TSNAs). Accurate prediction of TSNAs is key to generate potent TSNA specific vaccine approaches. Viral vector-based vaccine platforms have shown to induce hi-titer, polyfunctional and durable CD4+ and CD8+ T-cell responses in humans. The personalized vaccine is delivered in combination with immune checkpoint blockade, to keep TSNA-induced T-cells active in the immunosuppressive tumor microenvironment.

12:45 Close of Conference

* 주최측 사정에 따라 사전 예고없이 프로그램이 변경될 수 있습니다.