SC9: Companion Diagnostics for Immuno-Oncology

SUNDAY, MARCH 1 | 5:30 - 8:30 PM (DINNER PROVIDED)

ABOUT THIS COURSE:

As the field of Immuno-Oncology (IO) therapeutics evolves from one of monotherapy focused on PD-1 or PD-L1 targets into IO combination therapies including either 1) chemo/radio therapy or 2) novel therapeutic targets within the immune system, biomarker approaches to enrich for subjects most likely to respond to IO therapeutics have evolved also. This short course will review where we have been as a field regarding PD-L1 immunohistochemistry, microsatellite instability and DNA repair biomarkers, thinking forward to biomarkers of mutation burden which are still in development as potential companion diagnostic biomarkers.

COURSE AGENDA:

5:30 pm Intro to IO Diagnostic Biomarkers and PD-L1 IHC Evolution from TPS to CPS

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

Co-development of a diagnostic can be a little tricky and may complicate drug development, but it can be well worth the trouble. The PD-L1 companion diagnostic had a huge impact on pembrolizumab, making it the first immunotherapy approved as a first-line agent for non-small cell lung cancer. Adapting the PD-L1 diagnostic to incorporate immune cell expression facilitated approval of pembrolizumab for another five indications.

6:15 Dinner Buffet

6:45 MSI/MMR Testing: Pan Tumor Immunotherapy Development and the Start of Biomarker-Driven Indications

Mary J. Savage, Senior Director, Companion Diagnostics, GlaxoSmithKline

The achievement of biomarker-driven indications with approval of tumor-agnostic cancer therapeutics was led by approval of Keytruda in MSI-H/dMMR-selected populations. We will review this landmark approval and subsequent approvals and/or studies in progress that address biomarker selected/tumor-agnostic populations in IO or using other therapeutic modalities. Similarities and differences in these approaches will be included in the discussion.

7:30 HRD/TMB Testing: DNA Mutation Signatures, Present and Future Promise for Patient Selection

Lakshman Ramamurthy, PhD, Senior Director, Global Regulatory Affairs, Oncology, GlaxoSmithKline

An ever-growing understanding of the genetic basis and molecular heterogeneity of cancer has driven the development of targeted therapies and associated companion diagnostic tests that have provided significant benefit to patients. These advances in precision medicine have given rise to approvals of subsequent same-in-class therapeutic products each of which are, most often, paired with a different companion diagnostic test. The benefits of multiple therapeutic options offered by approvals of same-in-class therapeutic products, such as with biomarkers TMB and HRD, for IO and PARP inhibitors respectively, may be compounded by added complexity in Rx-CDx co-development in patient selection due to inconsistent biomarker definitions and self-described clinical testing workflows and practice. Status of precompetitive development of TMB diagnostics will be reviewed as well as well as current issues in HRD testing landscape

8:30 Course Ends

INSTRUCTORS:

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

Ken led Merck’s translational program which developed the “PD-L1 test,” defined the “TPS 50” tumor, and revolutionized the treatment of non-small cell lung cancer. The PD-L1 test, commercialized by Agilent, became the first FDA-approved companion diagnostic for immunotherapy, enabled Keytruda (pembrolizumab) to become “first to first line,” and thereby helped countless patients live longer. The translational program continued to advance cancer immunotherapy, and PD-L1 now is a companion diagnostic for Keytruda in six tumor types. Keytruda has become the foundation of Merck’s oncology program, Merck’s top-selling drug, and the leading anti-PD-1 drug in the industry (having begun 4-5 years behind its major competitor). In recognition of his contribution to patients and to the advancement of cancer immunotherapy, Dr. Emancipator received the 2019 Israel Davidsohn Distinguished Service Award and the 2017 Philip Levine Award for Outstanding Research from the American Society for Clinical Pathology (ASCP). He was one of 6 individuals to receive, on behalf of Merck, the 2015 PhRMA Research and Hope Award for research by a biopharmaceutical company. Dr. Emancipator received his AB degree from Harvard University and his MD from St. Louis University. He completed his medical internship at Westchester County Medical Center and his pathology residency at the State University of New York at Stony Brook. He has held appointments at the US National Institutes of Health, the US Food and Drug Administration, Cornell University, Beth Israel Medical Center, Bayer Healthcare, Siemens Healthcare, and Abbott Molecular prior to joining Merck. He also has held various leadership positions with ASCP, eventually becoming its Treasurer and serving on its Board of Directors. He is reviewer for the American Journal of Clinical Pathology.

Lakshman Ramamurthy, PhD, Senior Director, Global Regulatory Affairs, Oncology, GlaxoSmithKline

Lakshman leads the diagnostics global regulatory group at GSK, prior to which he was global regulatory lead at Foundation Medicine. He worked at the US FDA Center for Devices and Radiological Health (CDRH), variously, as Senior Reviewer leading the FDA- CMS Parallel Review pilot project, Acting Associate Director, Policy Advisor to the Office of Center Director CDRH and finally as Legislative Analyst in the Office of Commissioner on issues pertaining to FDASIA and user fees. From 2014-16, he was appointed member of CMS' Medicare Evidence Development and Coverage Advisory Committee (MEDCAC). Lakshman has a PhD in Molecular Biology from the University of North Carolina at Chapel Hill, followed by post-doctoral training in the Division of Hematology-Oncology at St. Jude Children's Research Hospital.

Mary J. Savage, Senior Director, Companion Diagnostics, GlaxoSmithKline

Mary graduated with a PhD in Pharmacology from Columbia University studying neuron injury and regeneration. She joined Cephalon, Inc. (now Teva Pharmaceuticals) to study Alzheimer's disease (AD) drug discovery and translational sciences research, including amyloid and secretase biology, with application to secretase inhibition, transgenic AD model development, and tau kinase inhibitor biology and drug discovery. Mary continued her study of Alzheimer’s disease at Merck, joining in 2006, where she led translational efforts on several amyloid beta-, apoE-, and tau-targeted drug discovery programs. In 2009, Mary shifted to become the lead for AD biomarker development, working with consortia including ADNI, ADNI PPSB and GBSC and leading to the application of patient enrollment biomarkers in two Phase III clinical trials of beta secretase inhibitor. In 2013, Mary joined the companion diagnostic group at Merck to develop biomarkers for Keytruda, including PD-L1 and Microsatellite Instability High (MSI-H) biomarkers. Her work has led to the US FDA approval of PD-L1 Agilent Pharm Dx IHC assay for selection of late line Gastric, Bladder and Esophageal cancer patients to receive Keytruda monotherapy, as well as the Japan PMDA approval of the FALCO PCR assay for MSI-H, also for patient selection to receive Keytruda monotherapy. Mary led Merck’s efforts to develop two companion diagnostic assays in the US for MSI-H (Next Generation Sequencing), and mismatch repair deficiency (Immunohistochemistry) prior to joining GlaxoSmithKline where she is leading companion diagnostic efforts for Zejula.

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