Cambridge Healthtech Institute’s Third Annual
Companion and Complementary Diagnostics in Immuno-Oncology
Predicting and Monitoring Response to Cancer Immunotherapy
August 16-17, 2017 | Grand Hyatt Washington | Washington, DC
Recent advances in cancer immunotherapy have generated excitement across all fields of oncology. When working, immune checkpoint inhibitors, and adoptive T-cell therapies create more sustainable results with less probability of recurrence than conventional or targeted cancer therapy. However, the field is still experiencing a lack of predictive biomarkers and companion/complementary diagnostics. Challenges in discovering predictive biomarkers for cancer immunotherapy involve multiple cell types, multiple mechanisms of T-cell regulation, genetic heterogeneity of tumors, immune components, etc. The companion and complementary diagnostics for immune modulating therapies are complicated and require a new systematic approach. Cambridge Healthtech Institute’s 3rd Annual Companion and Complementary Diagnostics in Immuno-Oncology conference is designed to bring together clinical immuno-oncologists, researchers from pharmaceutical and biotech companies, and members of the laboratory medicine community to discuss the underlying mechanisms of cancer immunotherapy, its predictive biomarkers as well as existing and emerging clinical assays aiming to improve patient outcomes.
Final Agenda
Recommended Short Course(s)*
SC10: Immune Monitoring Tools for Immuno-Oncology
*Separate registration required
WEDNESDAY, AUGUST 16
10:30 am Registration
1:05 pm Luncheon Presentation: Bridging Studies: A Reality in the Clinical Development of Diagnostic Associated Oncology Drug Programs
Dan Snyder, President & CEO, MolecularMD
Precision medicine efforts are yielding breakthrough therapy designations with accelerated approvals. Many of these programs utilize a Companion Diagnostic. Best demonstrated practices indicate that a bridging strategy needs to be deployed to manage risk and meet compressed NDA submission timelines. All codevelopment programs prefer to avoid a bridging study, but reality dictates that a plan is needed. Experiences with codevelopment and case studies will be shared with the audience.
1:35 Ice Cream and Cookie Break in the Exhibit Hall with Poster Viewing
2:05 Chairperson’s Opening Remarks
Michael C. Montalto, Ph.D., Executive Director, Translational Pathology & Biomarker Technologies, Translational Medicine, Bristol-Myers Squibb
2:10 Biomarker and Companion Diagnostics Strategy for Immuno-Oncology (IO) Combination Therapies
Katie Streicher, Ph.D., Associate Director, Translational Medicine, Medimmune
Anti-PD-1(L1) checkpoint inhibitors are approved for the treatment of multiple tumors. IO combinations with immune agonists and other checkpoint inhibitors are under investigation to enhance and broaden the benefits of immunotherapy, but how to prioritize the large number of potential combinations is not clear. We are using gene expression and image analyses of tumor biopsies to understand the tumor immune micro-environment, and as an aid in prioritizing IO combinations.
2:55 FDA Perspective on Translational Biomarkers in Immuno-Oncology
Soma Ghosh, Ph.D., Scientific Reviewer, Division of Molecular Genetics and Pathology, OIR, CDRH, FDA
With the rapid evolvement of immuno-oncology based therapies, it is important to develop robust and accurate in vitro diagnostic assays that translate well to the clinical setting. This talk will provide a brief overview of the current landscape of immuno-oncology based biomarker diagnostic assays, followed by a discussion of assay development and validation considerations to facilitate successful regulatory submissions of immuno-oncology companion diagnostics.
3:40 Companion Diagnostics for Immuno-Oncology: Global Commercial and Partnership Considerations
Joseph V. Ferrara, President, Boston Healthcare Associates
The testing paradigm in immuno-oncology is growing increasingly complex, moving beyond PD-L1, to include mismatch repair, microsatellite instability, tumor mutational burden, and others. The presentation will highlight 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.
3:55 The Insider’s Guide to Collecting Quality Human Biosamples and Essential Questions All Researchers Should Be Asking
Jon Wetzel, COO, TriMetis Life Sciences
Asking the right questions can lead to accelerated research. Jon Wetzel, COO of TriMetis Life Sciences, has over 21 years of assessing and auditing multiple biorepositories, biobanks, SOP’s and collection procedures. With over 6 of those years as a bench researcher and 15 years acquiring, processing and shipping samples, Jon has experienced first-hand the mistakes companies have made in acquiring these highly-sought after samples. He has taken his experience and is letting researchers in on the essential questions they need to ask to make sure that the samples they are using are going to give them the best experimental results possible.
4:10 Refreshment Break in the Exhibit Hall with Poster Viewing
5:00 Digital Pathology as a Next-Generation Biomarker Technology for Immuno-Oncology and Companion Diagnostics
Michael C. Montalto, Ph.D., Executive Director, Translational Pathology & Biomarker Technologies, Translational Medicine, Bristol-Myers Squibb
Digital pathology and image analysis plays an important role in drug development including tumor profiling, mechanisms of action, and patient selection. In immuno-oncology, understanding cell phenotypes in the context of the tumor micro-environment is critical and image analysis-based multiplexing can further shed light on the immune-biology of cancer. Clinical platforms for digital pathology are being established, which creates a practical path to transition image analysis-based biomarkers to companion diagnostics.
5:30 CO-PRESENTATION: Precision Immunotherapy: Next-Generation Biomarkers for Combination Therapies
Kenneth Emancipator, M.D., Executive Medical Director and Head of Companion Diagnostics, Translational Medicine, Merck
Scott Kopetz, M.D., Ph.D., Associate Professor, Department of Gastrointestinal Medical Oncology, MD Anderson Cancer Center
A predictive biomarker enabled Keytruda® (pembrolizumab) to become the first immunotherapy approved for first-line treatment of non-small cell lung cancer. The PD-L1 IHC 22C3 pharmDx®, the first FDA-approved companion diagnostic in cancer immunotherapy, was invaluable for identifying patients who benefit from Keytruda monotherapy. However, as Keytruda combinations (either with chemotherapy or with other immunotherapeutics) emerge, decision support will require additional, next-generation biomarkers, as a single biomarker may be inadequate.
6:00 Companion Diagnostics for Immunotherapy
David L. Rimm, M.D., Ph.D., Professor, Pathology, Yale University
Immunotherapy has changed the therapeutic landscape in lung cancer, and it has led to the first new IHC companion diagnostic test in over 10 years. Here we will examine the existing companion diagnostic tests and consider their accuracy, concordance, and likelihood of long term value for prediction of response to immune-oncology therapies.
6:30 Close of Day
6:30 Dinner Short Course Registration
6:45-9:15 pm Recommended Dinner Short Course(s)*
SC13: Regulatory and Reimbursement Issues with Advanced Diagnostics and Circulating Biomarkers
*Separate registration required
THURSDAY, AUGUST 17
7:30 am Problem-Solving Breakout Discussions with Continental Breakfast
Next-Generation Biomarker Technology for Immuno-Oncology and Companion Diagnostics
Moderator: Michael C. Montalto, Ph.D., Executive Director, Translational Pathology & Biomarker Technologies, Translational Medicine, Bristol-Myers Squibb
- What are the most promising and immediate “next generation” technologies for companion diagnostics?
- Next generation sequencing platforms, IHC multiplexing, Circulating tumor cells, other
- What are the limitations and challenges of bringing these technologies to the clinic?
- Technical, Regulatory, Commercial, Reimbursement, Education and awareness
- What technologies are further out, but hold the most promise and why?
Regulatory Perspectives for IO
Moderator: Janaki Veeraraghavan, Ph.D., Senior Staff Fellow, FDA
- Regulatory Updates
- Recent Approvals
- Common Challenges
8:25 Chairperson’s Opening Remarks
Phillip Zack Brohawn, Ph.D., Associate Director, MedImmune
8:30 Application of Next-Generation Sequencing in Drug Development
Phillip Zack Brohawn, Ph.D., Associate Director, MedImmune
Advances in the field of next generation sequencing, particularly with respect to an expanded menu of applications, have led to integration of the technology in the drug development space. The practical application of these evolving techniques throughout multiple steps of the drug development process will be discussed, along with practical examples of applications to shed light on the current and evolving use of this technology in drug development.
9:00 Tumor Mutational Burden as a Biomarker for Immunotherapy: A Summary of Clinical Evidence
David Fabrizio, Leader, Cancer Immunotherapy, Foundation Medicine
Reliable, quantifiable biomarkers capable of predicting response to checkpoint inhibitor therapies represent a significant clinical need. Tumor mutational burden (TMB) determination from comprehensive genomic profiling has emerged as a potential solution. Herein, we summarize the clinical utility of TMB calculated from the FoundationOne comprehensive genomic profiling test in more than 500 patients across five disease types, including urothelial bladder carcinoma, non-small cell lung cancer, and metastatic melanoma, with case reports in glioblastoma and colorectal cancer.
9:30 Comprehensive Immune Profiling using NGS: Measuring More to Guess Less
Mary Nesline, Senior, Vice President, Knowledge Informatics, OmniSeq Inc.
Given the ever-increasing number of combinatorial immunotherapeutic regimens tested in clinical trials today, the selection of combination partners is often not rationally guided. There is a need to accurately assess the tumor microenvironment using patient FFPE archival samples to determine the best combination immunotherapy for that patient, i.e. precision immunotherapy. A New York State approved NGS assay that detects several known markers of the host anticancer immune response will be discussed. This comprehensive assay, utilizes DNA and RNA-seq providing both mutational burden and comprehensive gene expression profiling of tumor infiltrating lymphocytes (TILs) and T-cell receptor signaling in solid tumors.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
11:00 PD-L1 IHC Assay Comparison in Lung Cancer: The Blueprint Project
Fred R. Hirsch, M.D., Ph.D., Professor of Medicine and Pathology, Pia and Fred R. Hirsch Endowed Chair, University of Colorado Cancer Center; CEO, International Association for the Study of Lung Cancer (IASLC)
Immunotherapy is very encouraging in lung cancer and approved therapy both for first line treatment as well as for patients, who previously have progressed on chemotherapy for advanced NSCLC. PD-L1 IHC has been pursued in clinical trials as a selection assay, and one assay (Dako 22 C3) has been approved as “companion diagnostics” for pembrolizumab, while two other assays are approved as “complementary diagnostics”; Dako 28-8 for nivolumab and Ventana SP-142 for atezolizumab. All the PD-L1 IHC assays are unique in terms of antibody (and staining platform) used. The IASLC is coordinating the “PD-L1 IHC Comparison Blueprint Project”, which compares the analytical performances of all the assays.
11:30 Companion and Complementary Diagnostics for Cancer Immunotherapy: Regulatory Perspective
Janaki Veeraraghavan, Ph.D., Senior Staff Fellow, FDA
The talk will provide an update on current companion and complementary diagnostics in cancer immunotherapy and provide examples of regulatory review issues and pathways to plan for CDx pre market applications.
12:00 pm PANEL DISCUSSION: Companion Diagnostics for Cancer Immunotherapy: Beyond PD-L1
Moderator:
David L. Rimm, M.D., Ph.D., Professor, Pathology, Yale University
- Latest advances in overcoming tumor-induced immune suppression and immune escape
- Standardization of existing assays and approaches
- Clinical trials for cancer immunotherapy: specific features and the role of diagnostics
Panelists: Fred R. Hirsch, M.D., Ph.D., Professor of Medicine and Pathology, Pia and Fred R. Hirsch Endowed Chair, University of Colorado Cancer Center; CEO, International Association for the Study of Lung Cancer (IASLC)
Janaki Veeraraghavan, Ph.D., Senior Staff Fellow, FDA
J. Joseph Melenhorst, Ph.D., Director, Product Development & Correlative Sciences Laboratories (PDCS); Adjunct Associate Professor, Center for Cellular Immunotherapies, University of Pennsylvania
12:30 Sponsored Presentation (Opportunity Available)
1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:30 Session Break
2:00 Chairperson’s Remarks
Alan L. Epstein, M.D., Ph.D., Professor, Pathology, Keck School of Medicine, University of Southern California
2:05 Translational Cycles in Adoptive T-Cell Therapies
J. Joseph Melenhorst, Ph.D., Director, Product Development & Correlative Sciences Laboratories (PDCS); Adjunct Associate Professor, Center for Cellular Immunotherapies, University of Pennsylvania
Targeting tumors using the patient’s own T cells redirected using a synthetic CD19-directed chimeric antigen receptor (CART19) has proven tremendously effective in various B cell malignancies. Clinical observations and correlative studies have provided insight into the on-target efficacy and predictive biomarkers, and on-target/on- and off-tumor toxicities which help guide future iterations of CAR-redirected T cell therapies. My talk will highlight the latest findings in CAR T cell trials at the University of Pennsylvania and at other institutions, and provide insight into the various processes associated with this novel form of immunotherapy, some of which may lead to the development of diagnostic tests.
2:35 Developing an Integrated Translational Science Strategy to Support Clinical Development of Novel Immunotherapies
Heather A. Hirsch, Ph.D., Director of Bioinformatics, Translational Sciences, Jounce Therapeutics
Jounce is developing JTX-2011, an agonist antibody to the co-stimulatory molecule ICOS (Inducible CO-Stimulator of T cells). Preclinical studies demonstrated efficacy in syngeneic tumor models, with enhanced efficacy in combination with PD-1 inhibitors. JTX-2011 induces T effector cell activation and also preferentially reduces T regulatory cells in the tumors. This dual mechanism contributes to the significant anti-tumor response observed in preclinical models. A promising safety profile was revealed in preclinical studies. JTX-2011 is in clinical development as a monotherapy and in combination with anti-PD-1 therapy
3:05 Role of HLA Expression in Tumors for Successful Adaptive Immunotherapy
Alan L. Epstein, M.D., Ph.D., Professor, Pathology, Keck School of Medicine, University of Southern California
A major mechanism of immune escape is the loss of HLA Class I expression on the surface of solid tumors. Roughly 50% of all tumors induce this mechanism either post-transcriptionally (soft) or by gene deletion (hard) to dampen immune intervention and active immunotherapy. Treatment with TLR agonists, small molecules, and cytokines to reactivate HLA Class I expression in cases having soft inactivation may be critical for successful immunotherapy.
3:35 MRI Imaging Changes following Immunotherapy in Patients with Prostate Cancer
Ravi A. Madan, M.D., Associate Research Physician, Genitourinary Malignancies Branch, Clinical Director, Genitourinary Malignancies Branch, NIH/NCI
As immunotherapy continues to evolve in the clinical setting, there is still an unmet need for biomarkers that predict or define responses. We have recently completed a clinical trial with immunotherapy and radiation in newly diagnosed prostate cancer. Preliminary data suggests that the immune-based combination was associated qualitative MRI changes that corresponded to changes in immune cell subsets. These data may have application beyond prostate cancer in defining response to immune therapy.
4:05 Close of Conference
4:30 Symposia & Short Course Registration
RECOMMENDED CONFERENCE SYMPOSIUM:
Emerging Cancer Biomarkers
Separate registration required