Recent advances in cancer immunotherapy have generated excitement across all fields of oncology. When working, immune checkpoint inhibitors, cancer vaccines, and adoptive T-cell therapies create more sustainable results with less probability of recurrence than conventional or targeted cancer therapy. However, can we predict when it will work and do we know how to monitor patients’ response? Challenges in discovering predictive biomarkers for cancer immunotherapy are very significant and involve multiple cell types, multiple mechanisms of T-cell regulation, genetic heterogeneity of tumors, immune components, etc. Many industry and academia researches are fighting these odds right now, and they would benefit from a productive discussion and knowledge exchange. Cambridge Healthtech Institute’s Second Annual Diagnostics to Guide Cancer Immunotherapy 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.

WEDNESDAY, AUGUST 24

10:30 am Registration

11:15 PLENARY KEYNOTE SESSION

12:50 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:25 Ice Cream and Cookie Break in the Exhibit Hall with Poster Viewing

KEYNOTE SESSION: FROM PREDICTIVE BIOMARKERS TO COMPANION DIAGNOSTICS

1:50 Chairperson’s Opening Remarks

Kenneth Emancipator, M.D., Executive Medical Director and Head, Companion Diagnostics, Merck Research Laboratories

2:00 Improving Immunotherapy for Cancer by Core Analysis

James L. Gulley, M.D., Ph.D., Chief, Genitourinary Malignancies Branch, Director, Medical Oncology Service, Center for Cancer Research, NCI, NIH

Immunotherapy has demonstrated rapid, deep, and durable responses across a wide array of different cancers. However these remarkable responses have only been seen in a small subset of patients. Combinations of agents that can initiate an immune response with agents that can render immune cells more functional within the tumor have the potential to further improve outcomes. However key to this is an understanding of immune regulatory influences within the tumor microenvironment.

2:45 The Immunoproteasome is a Key Regulator of Immune Evasion

Sam M. Hanash, M.D., Ph.D., Professor, Molecular Pathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center

Antigen presentation by tumor cells is largely dependent on the immunoproteasome. Assessment of the status of the immunoproteasome may predict response or resistance to immunotherapeutic modalities.

3:30 A Cost-Effective GMP Platform for the Manufacture of Companion Diagnostic Proteins

Scott Waniger, Vice President, BioServices, Cell Culture Company

Manufacturing small quantities of GMP biologics for IVDs cost effectively is difficult. One solution is the use of a scalable, single-use perfusion bioreactor. In this presentation, a comparison of bioreactors for production of IVDs will be given. Data will be presented showing scalability and the ability to maintain steady-state production.

3:45 Circulating Stromal Cells for Immunotherapy

Daniel Adams, Senior Research Scientist, Creatv MicroTech Inc

Circulating Stromal cells and Circulating Tumor cells present in the blood of patients with solid tumors are easily isolated using CellSieveTM microfilters, useful for non-invasive sequential tumor monitoring. With the ability to stain >12 clinically relevant biomarkers, this technique is ideal for targeted drug analysis, combination immunotherapy and companion diagnostics.

4:00 Refreshment Break in the Exhibit Hall with Poster Viewing

4:45 Determinants of Sensitivity and Resistance to Immune Checkpoint Blockers in Cancer 

Kurt A. Schalper, M.D./Ph.D. Assistant Professor of Pathology and Medicine (Medical Oncology), Yale School of Medicine, Director, Translational Immuno-oncology Laboratory, Yale Cancer Center

Immune checkpoint blockers have emerged as effective anti-cancer immunotherapy against various tumor types. Diverse studies have identified biomarkers associated with clinical benefit to these therapies. However, the clinical use of such tests is limited by their variable performance and restricted understanding of their biological significance. Here, we will discuss the current state and future landscape of immunotherapy biomarkers with focus in non-small cell lung cancer.

5:15 Precision Immunotherapy: The Challenge of Converting Complex Predictive Biomarkers into Practical Companion Diagnostics

Kenneth Emancipator, M.D., Executive Medical Director, Head of Companion Diagnostics, Merck Research Laboratories

Early immunotherapies have produced dramatic results for some patients, but future immunotherapies likely need to be guided by diagnostics to benefit more patients. Properly targeting immunotherapy requires incorporating into clinical practice complex diagnostics which can assess host immune response in addition to cancer biology itself. “Precision Immunotherapy” requires discovery of appropriate predictive biomarkers and incorporating them into practical companion diagnostics which will be adopted by practitioners.

5:45 PANEL DISCUSSION: Companion Diagnostics for Cancer Immunotherapy: Beyond PD-L1

Moderator:
Kenneth Emancipator, M.D., Executive Medical Director and Head, Companion Diagnostics, Merck Research Laboratories

James L. Gulley, M.D., Ph.D., Chief, Genitourinary Malignancies Branch, Director, Medical Oncology Service, Center for Cancer Research, NCI, NIH
Kurt A. Schalper, M.D./Ph.D. Assistant Professor of Pathology and Medicine (Medical Oncology), Yale School of Medicine, Director, Translational Immuno-oncology Laboratory, Yale Cancer Center

• 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

6:15 Close of Day

6:00 Dinner Short Course Registration*

*Separate registration required

THURSDAY, AUGUST 25

NOVEL APPROACHES: NEOANTIGENS, EPIGENETICS AND MORE

8:25 Chairperson’s Remarks

David L. Rimm, M.D., Ph.D., Professor, Pathology, Yale University

8:30 Companion Diagnostics for Cancer Immunotherapy

David L. Rimm, M.D., Ph.D., Professor, Pathology, Yale University

Companion diagnostic testing for PD-1 axis immunotherapy has been a challenge. Multiple assays to test for the same variable (PD-L1) and other mechanisms for assessing the immunologic state of the tumor and its environment are all being tested. This session will discuss issues related to both PD-L1 assays and also discuss progress toward prediction of patient benefit from immune therapy, including assays that are not in the drug labels.

9:15 PD-1 Blockade in Tumors with Mismatch-Repair Deficiency

Luis Diaz, M.D., Associate Professor, Oncology & Cancer Biology, Johns Hopkins University

Somatic mutations have the potential to encode “non-self” immunogenic antigens. Tumors with a large number of somatic mutations due to mismatch-repair defects appear to be highly susceptible to immune checkpoint blockade. This presentation will summarize the clinical and genomic data of using mutations as neoantigens.

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

10:50 Epigenetic Priming for Immunotherapy in Breast Cancer

Pamela N. Munster, M.D., Professor, Medicine; Program Leader, Development Therapeutics; Director, Early Phase Clinical Trials’ Program, Helen Diller Cancer Center, University of California, San Francisco

A breakdown in immune tumor surveillance plays a crucial role in the development of metastatic cancer. Targeting the programmed death receptor (PD-1) and its ligand (PD-L1) have been major breakthroughs. In breast cancers however, particularly in hormone-driven breast cancer, immune responses are often absent. In reverse-translating clinical findings, from the patient to preclinical models, we show that epigenetic modulation leads to epigenetic immune priming and enhancement of immune response.

11:20 Cancer Neoantigens and Their Role as Predictive Biomarkers for Cancer Immunotherapy

Rajarsi Mandal, M.D.,Head and Neck Surgical Oncology, Memorial Sloan Kettering Cancer Center

Ultimately for the adaptive immune system to combat a cancer, it must recognize it as foreign. Pre-clinical work has suggested mutations in a tumor lead to the formation of neo-antigens (novel peptides) that the immune system recognizes as foreign. Increased mutational load in a number of malignancies has been associated with improved response to checkpoint blockade, suggesting that an increase in neo-antigens leads to a stronger likelihood of response. We will review mutational load and neo-antigen-based signatures as predictors of response to checkpoint blockade.

11:50 Immunosequencing: Generating a Potential New Class of Diagnostics

  Catherine M. Sanders, MT, Ph.D, Director, Team Lead, Scientific Liaison, Adaptive Biotechnologies Corp.

Adaptive Biotechnologies’ immunosequencing technology combines bias-controlled multiplex PCR amplification with high-throughput sequencing and sophisticated bioinformatics. Adaptive’s immunoSEQ® Assays enable the accurate profiling of T cell and B cell receptor repertoires. In solid tumors, the immunoSEQ Assay accurately quantifies the density and clonality of tumor infiltrating lymphocytes, with preclinical and clinical applications to inform repertoire changes in response to single agent or combination immunomodulatory therapies that have potential prognostic and predictive value.

12:20 pm Deciphering the Biology that Drives Response to Immunotherapy

Cliff Hoyt, Oncology Fellow, Director Lab Services and Applications, Quantitative Pathology, PerkinElmer

12:50 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:20 Session Break

PD-L1 AND BEYOND

2:00 Chairperson’s Remarks

Janis M. Taube, M.D., MSc, Johns Hopkins University School of Medicine

2:05 Hitting the Target: CAR T-Directed EGFRvIII in Glioblastoma

Jennifer Morrissette, Ph.D., Scientific Director, Clinical Cytogenetics Laboratory; Clinical Director, Center for Personalized Diagnostics (CPD), University of Pennsylvania School of Medicine

We initiated a pilot study of autologous T cells re-directed to the EGFR variant III mutation by means of a lentiviral vector encoding a chimeric antigen receptor (CAR). GBM tumors were screened for the presence of the EGFRvIII mutation by a next-generation sequencing based assay with eligible patients enrolled in the study. NGS results of those patients who have had pre- and post-infusion studies will be discussed.

2:35 Combining PD-L1 Status with Additional Predictive Factors for Cancer Immunotherapy Response

Janis M. Taube, M.D., MSc, Director, Dermatopathology; Associate Professor, Dermatology and Pathology, Johns Hopkins University School of Medicine

Immune resistance by tumor may have both adaptive and constitutive components, and both have mechanistic and biomarker implications. This talk will discuss our ongoing efforts to characterize further the local tumor microenvironment with the aim of improving patient selection and developing rational treatment combinations to overcome adaptive immune resistance.

3:05 Clinical Advances with Anti-PD-1 Inhibition and Combination Immunotherapy Strategies

Geoffrey T. Gibney, M.D., Georgetown-Lombardi Comprehensive Cancer Center

Recent immunotherapy developments targeting the PD-1/PD-L1 axis have led to a new era in the management of patients with advanced malignancies. Combination regimens, such as concurrent anti-PD-1 and anti-CTLA-4 agents, have demonstrated even greater clinical activity than monotherapy, but convey a higher risk of severe immune toxicities. New combination strategies and biomarker research are expected to lead to personalized approaches. The current status of anti-PD-1 therapies will be reviewed.

3:35 PANEL DISCUSSION: Enabling Immune Checkpoint Inhibitors Therapy

Moderator:
David L. Rimm, M.D., Ph.D., Professor, Pathology, Yale University

Panelists: Speakers of the Day

• Discover novel immune checkpoints as antibody targets for cancer immunotherapy
• Validate predictive biomarkers
• Design and validate clinical assay

4:05 Close of Conference