Cambridge Healthtech Institute’s 3rd Annual

Immuno-Oncology Biomarkers 2: Predictive Biomarkers and Companion Diagnostics

August 28-29, 2018

As pharmaceutical and biotechnology companies increase their investment in immuno-oncology programs to facilitate rapid development of novel immunotherapies, there is increasing pressure to discover and validate relevant biomarkers. Cambridge Healthtech Institute’s Third Annual Immuno-Oncology Biomarkers 2: Predictive Biomarkers and Companion Diagnostics meeting will bring together biomarkers experts from industry and academia to address rapid development of predictive and prognostic IO biomarkers, utility of these biomarkers in clinical trials, and their potential as companion diagnostics.


Final Agenda

TUESDAY, AUGUST 28

12:00 pm Registration

BIOMARKERS TO PREDICT RESPONSE TO IMMUNOTHERAPY

1:25 Chairperson’s Opening Remarks

George Poste, DVM, PhD, Chief Scientist, Complex Adaptive Systems, Arizona State University


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

George Poste, DVM, PhD, Chief Scientist, Complex Adaptive Systems, 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 Molecular Mechanisms and Biomarkers Predictive of Response to Keytruda

Andrey Loboda, PhD, Director, Genetics and Pharmacogenomics, Merck

The talk will address molecular biomarkers of response to pembrolizumab, including the role of tumor antigenicity, as measured by mutational load (ML) and T cell inflamed microenvironment in predicting the response to pembrolizumab. Data will be presented that prospectively validates the utility of both biomarkers as tumor type agnostic and orthogonal measures of response. These findings provide a biomarker framework for development of pembrolizumab as a monotherapy and for characterizing responses to novel immunotherapy regimens.

2:30 Tissue-Based Diagnostic Tests for Immunotherapy

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

While it would be great to be able to predict response to immunotherapy without a biopsy, to date, other modalities including circulating tests and imaging approaches cannot match the sensitivity and specificity of tissue-based tests. Here we will take a closer look at the predictive value of PD-L1 by immunohistochemistry including the tumor vs. the immune cell components as well as other protein-based tests.

3:00 Sponsored Presentation (Opportunity Available)

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


4:15 PLENARY KEYNOTE SESSION

4:20 CAR-T Therapy for B Cell Malignancies

Jennifer Brogdon, PhD, Director, Exploratory Immuno-Oncology, Novartis

 

4:55 Walking on the Moon: Reflections on the Work of the Cancer Moonshot and the Future of the Biden Cancer Initiative

Gregory C. Simon, JD, President, Biden Cancer Initiative

 

5:30 Welcome Reception in the Exhibit Hall with Poster Viewing

5:30 Dinner Short Course Registration*

*Separate registration required.

6:30 End of Day

6:30-9:00 pm Dinner Short Course

SC1: Bioinformatics for Immuno-Oncology and Translational Research

6:30-9:00 pm Dinner Short Course

SC2: Next-Generation Immunotherapies: Part 1

WEDNESDAY, AUGUST 29

7:30 am Morning Coffee

TRANSLATING GENOMIC IO BIOMARKERS TO COMPANION DIAGNOSTICS: MISMATCH REPAIR AND TUMOR MUTATIONAL BURDEN

8:25 Chairperson’s Remarks

Robert Anders, MD, PhD, Associate Professor, Pathology, Johns Hopkins University


8:30 FEATURED PRESENTATION: Predictive Biomarkers in Colon Cancer and Mismatch Repair Deficient Tumors

Robert Anders, MD, PhD, Associate Professor, Pathology, Johns Hopkins University

Human cancer tissue samples have been and will be an excellent platform to uncover predictive biomarkers to select a patient for immune based chemotherapy. This lecture will focus on looking back at what biomarkers lead to the success of PD-1/L1 blockade in colon cancer and mismatch repair deficient cancers. Emphasis will be on the lessons that were learned from these clinical trials and how those lessons can be applied moving forward.

9:00 The First Biomarker-Defined Tumor Indication: FDA Approval of Pembrolizumab for MSI-High Cancer

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

The program presents an overview of microsatellite instability (MSI) and mismatch repair defect (MMRD), and how it fits into the tumor immunogenicity-inflammation pathway. It reviews the history and clinical evidence for MSI and MMRD as a predictive biomarker for response to pembrolizumab. It discusses the unprecedented – and unorthodox – path to FDA approval of pembrolizumab. Finally, it discusses MSI and MMRD in the broader context of biomarkers in immuno-oncology.

9:30 Presentation to be Announced

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

10:45 The Return of Precision Medicine in Immuno-Oncology

Zhen Su, MD, MBA, Senior Vice President & CMO, NA, EMD Serono, Inc.

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.

11:15 Tumor Mutational Burden Testing for Patient Selection: Implementation of TMB Testing in the Real World

George A. Green, IV, PhD, Head, Pharmacodiagnostic Center of Excellence, Bristol-Myers Squibb

Tumor mutational burden (TMB), the frequency of somatic mutations in the tumor, is an emerging biomarker that predicts responses to immunotherapy. Tumors with high TMB may express novel protein sequences leading to the formation of neoantigens, and are believed to make the tumor more visible to the immune system. This may induce tumor-specific T cell responses that can be enhanced by checkpoint inhibitors. TMB is measured using next-generation sequencing, enabling assessment of hundreds of pre-specified genes. Discussion will provide insight into the rationale behind using TMB and practical considerations for its implementation.

11:45 The Cancer Genome’s Influence on Immunotherapy

Nadeem Riaz, MD, Associate Director, Immunogenomics and Precision Oncology Platform, Radiation Oncology, Memorial Sloan Kettering Cancer Center

Will review data showing the importance of tumor mutation burden in predicting outcomes to checkpoint blockade therapy. Will subsequently discuss emerging genetic features associated with response to therapy including microsatellite instability, HLA genotype, tumor clonality, and neo-antigen modeling amongst others.

12:15 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:45 Session Break

BIOMARKERS FOR CHECKPOINT INHIBITORS AND COMBINATIONS

1:40 Chairperson’s Remarks

Emmett Schmidt, PhD, Distinguished Scientist & Executive Director, Merck Research Labs

1:45 Emerging Biomarker Strategies in the Era of PD-1 Checkpoint Combination Therapies

Emmett Schmidt, PhD, Distinguished Scientist & Executive Director, Merck Research Labs

PD-1 checkpoint inhibition demonstrates unusually broad monotherapy activity across tumor types. Addressing the unmet medical need of patients not responding to checkpoint monotherapy can be achieved by finding highly effective combination therapies, by finding predictive biomarkers or a combination of both strategies. Biomarker strategies will need to evolve to accommodate the emerging landscape of broadly active PD-1 combination therapies.

2:15 Taking Immune-Oncology beyond Checkpoint Blockade

Marc Pelletier, PhD, Investigator II, Translational Immune Oncology, Novartis Institutes for Biomedical Research

Cancer treatment has been revolutionized by the success of checkpoint blockade in the clinic. In order to expand the pool of responsive patients, clinical trials are focused on combining checkpoint blockade with other immune modulating mechanisms. Critical to this success is the elucidation of biomarkers that presage response or highlight potential therapeutic combinations. TGFβ antagonism offers potential combination benefit and biomarker assessment for clinical development of this target will be discussed.

2:45 Presentation to be Announced

3:15 Refreshment Break in the Exhibit Hall with Poster Viewing

4:00 Biomarkers to Assess Efficacy and Toxicity of Immune Checkpoint Immunotherapies in Patients with Melanoma

Philip Friedlander, MD, PhD, Assistant Professor, Medicine, Hematology & Medical Oncology; Director, Melanoma Medical Oncology Program, Icahn School of Medicine at Mount Sinai

The use of anti-CTLA-4 and anti-PD-1 inhibitors to treat stage IV melanoma confers survival benefit. Limitations include the development of response in a subset of patients and the development of immune mediated toxicity. Identifying biomarkers’ predicting response or toxicity can optimize treatment choice and minimize toxicity risk. Biomarkers may reflect tumor or blood based characteristics. The identification and validation of whole-blood RNA transcript based gene signatures is a potential strategy.

4:30 Applying Next-Generation Sequencing to Assess Immune-Mediated Drug Hypersensitivity

Masahide Yano, PhD, Research Scientist, Center for Drug Evaluation and Research, FDA

Drug hypersensitivity remains a major clinical problem especially due to its unpredictable outcome in preclinical standard toxicity tests, which often causes patients’ morbidity. A goal of this study is to understand immunological mechanisms that underlie severe adverse drug reactions. To achieve this, we employed next-generation sequencing technology to identify a defined repertoire of CD8+ T cell receptors that recognize complexes of HLA/peptide/drug, and investigated their biological functions.

5:00 Prognostic and Predictive Markers for Immunotherapy and Combination Therapy

Kathleen M. Mahoney, MD, PhD, Clinical Instructor, Beth Israel Deaconess Medical Center; Research Fellow, Dana-Farber Cancer Institute

5:30 Dinner Short Course Registration*

*Separate registration required.

5:30 Close of Immuno-Oncology Biomarkers 2: Predictive Biomarkers and Companion Diagnostics

6:00-9:00 pm Dinner Short Course

SC3: Next-Generation Immunotherapies: Part 2

#IOSummit