Cambridge Healthtech Institute’s 5th Annual
Combination Immunotherapy
Targeting Immunotherapy Combinations for Increased Clinical Efficacy
11-12 March 2020
Treating patients with an immunotherapy combination has become commonplace for many cancers. With an abundance of combinations to choose from and plenty more clinical trials ongoing, it is difficult to know which combinations will be most effective. Whether
double immunotherapy combinations or immune checkpoint inhibitors combined with conventional cancer therapy, there are numerous factors that may influence therapeutic success, with varying degrees of supporting evidence. Predictive biomarkers, neoantigens,
therapeutic mechanism, reducing toxicity and the immune response are all important considerations. Join us for the 5th Annual Combination Immunotherapy conference and target immunotherapy combinations for increased clinical efficacy.
Final Agenda
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WEDNESDAY 11 MARCH
11:15 Organizer’s Remarks
Joel Hornby, BSc Hons, Conference Director, Cambridge Healthtech Institute
11:20 Chairperson’s Remarks
Reno Debets, PhD, Professor, Laboratory of Tumor Immunology, PI, Medical Oncology, Erasmus MC-Cancer Institute
11:30 Strategies to Improve Antitumor Efficacy of Genetically Engineered T Cells**
Stanley Riddell, MD, Scientific Director, Clinical Research, Fred Hutchinson Cancer Research Center; Professor, University of Washington School
of Medicine
Immune cells can be readily genetically modified to express natural tumor targeting antigen receptors or synthetic chimeric antigen receptors (CARs) that activate immune cell signaling pathways to result in destruction of tumor cells expressing the
relevant target molecule. The presentation will discuss advances in our understanding of receptor signaling and the development of strategies that combine therapeutic agents to improve efficacy and safely extend the spectrum of cancers that can
be treated with cell therapies.
12:00 PD-1 Antibodies Are Transforming Cancer Treatment
Kandeepan Ganeshalingam, MD, Executive Director,Therapeutic Area Head Oncology, European Clinical Development
Global Clinical Development, MRL, Merck Sharp & Dohme (MSD)
PD-1 antibodies have shown significant activity as monotherapy across multiple cancer types and lines of therapy. Precision medicine tools have been used to identify subjects most likely to respond to PD-1 antibody monotherapy, to provide insight
to potential resistance mechanisms, and to inform combination therapies. A number of these combinations have demonstrated significant activity in additional tumor types and lines of therapy.
12:30 Enjoy Lunch on Your Own
13:30 Chairperson’s Opening Remarks
To be Announced
Jakob Dupont, MD, MA, CMO, Gossamer Bio
13:35 KEYNOTE PRESENTATION: Developing PD-1 Combinations**
Gordon J. Freeman, PhD, Professor of Medicine, Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School
14:05 GB1275: A First-in-Class CD11b Modulator in the Clinic to Target Tumor Myeloid Suppressor Biology**
Jakob Dupont, MD, MA, CMO, Gossamer Bio
Immune checkpoint inhibitor therapy, such as antibodies targeting PD1 and PDL1, help a percentage of patients with cancer. However, tumors have a number of other mechanisms to escape immune surveillance. Myeloid suppressor cells (like MDSCs and TAMs)
present in colorectal, pancreatic, prostate, and triple negative breast cancers, are thought to be important to prevent checkpoint inhibitor activity. GB1275 is a first-in-class CD11b modulator in the clinic that targets myeloid suppressor cells.
GB1275 is being studied in selective solid tumors as monotherapy, in combination with either checkpoint inhibitor or chemotherapy.
14:35 Immune Contexture in the Era of Combination Immunotherapy**
Jerome Galon, PhD, Director of Research, INSERM UMRS1138, Cordeliers Research Center
The combination of immune parameters associating the nature, density, functional immune orientation and location of immune cells within the tumor, defined as the “immune contexture”, is associated to patients’ prognosis. Based on
these results, a standardized digital-pathology-based immune stratification-system, termed “Immunoscore”, was developed, having a prognostic power superior to that of the currently used TNM-classification system. The predictive value
of the Immunoscore for response to immunotherapy will be discussed.
15:05 Refreshment Break in the Exhibit Hall with Poster Viewing
15:40 Chairperson’s Opening Remarks
To be Announced
Khalid Shah, MS, PhD, Vice Chair of Research, Department of Neurosurgery Director, Center for Stem Cell Therapeutics and Imaging Director, Brigham and Women's Hospital, Harvard Medical School
15:45 Gene Edited and Engineered Stem cells and Immune cells: Opening New Venues in Cell Based Therapies for Cancer**
Khalid Shah, MS, PhD Vice Chair of Research, Department of Neurosurgery Director, Center for Stem Cell Therapeutics and Imaging Director, Center for Excellence in Biomedicine Brigham and Women's Hospital Associate Professor, Harvard Medical
School Principal Faculty, Harvard Stem Cell Institute BWH, Harvard Medical School
Cell based therapies are emerging as a promising strategy for cancer. We and others have developed cell surface receptor targeted adult stem cells, cancer cells and T cells expressing novel bi-functional immunomodulatory proteins. Using recently established
tumor models that mimic clinical settings, we have explored the fate and efficacy of different engineered cell based therapies. Our findings demonstrate the strength of using innovative approaches and clinically relevant preclinical models that
pave a path for clinical translation. This presentation provides data and rationale for assessing combined cell based studies in preclinical studies and translating the most promising studies into the clinic.
16:15 Immunotherapy with Avb6 Integrin Targeted CAR T Cells, Directed by CXCR2-Specific Chemokines
John Maher, MD, Consultant, Immunology, Kings College London
Avb6 integrin is aberrantly expressed in a broad range of solid tumours. This presentation will describe the iterative optimization of an Avb6-specific CAR, employing the CXCR2 chemokine receptor to enhance trafficking to IL-8 producing tumours and
enhancing signalling potency using a parallel CAR platform technology.
16:45 The Role of Autologous Natural Killer Cells in Combination with Immune Checkpoint Inhibitors and Antibodies in Cancer**
Paul Song, MD, CMO, Translation Medicine, NKMax America
Natural killer cells play a big role in the antibody-dependent cell-mediated cytotoxicity (ADCC) pathway and have also been identified as a key component in the responsiveness of tumors to checkpoint inhibitors. We discuss our proprietary natural
killer cell technology and our preclinical and clinical experience in ADCC and immune checkpoint-based therapy.
17:15 Problem Solving Breakout Discussions (See complete list of Problem-Solving Breakout Discussion)
What Are the Mechanisms of Immune Exclusion and What We Need to Know About Them?
Moderator:
Franco Marincola, PhD, Chief Scientific Officer, Refuge Biotechnologies
- Discuss the kind of barriers that prevent T cells from infiltrating tumors
- Physical barriers
- Functional barriers
- Dynamic barriers
How do we Effectively Develop Immunotherapy Combinations for Cancer?
Moderator: Johan Lantto, PhD, Project and Portfolio Director, Immuno-Oncology, Symphogen
Immunotherapy has shown impressive results in various cancer indications, however, only a subset of patients respond to single agent therapy.Combination immunotherapy presents an opportunity for improving responses and outcomes for cancer patients.The development of immunotherapy combinations faces a number of preclinical, clinical and regulatory challenges, which will be discussed in the breakout session.
18:15 Dinner Short Course Registration
18:45 Dinner Short Course
Recommended Short Course*
Dinner SC3: Engineering of Bispecific Antibodies and Multi-Specific Non-Antibody Scaffolds - LEARN MORE
Mathieu Cinier, PhD, Scientific Director, Affilogic
Mattias Levin, PhD, Senior Scientist, Antibody Engineering, Alligator Bioscience AB
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THURSDAY 12 MARCH
8:00 Registration and Morning Coffee
8:30 Chairperson’s Remarks
To be Announced
John Bell, PhD, Senior Scientist, Innovative Cancer Therapeutics, Ottawa Hospital Research Institute
8:35 Oncolytic Viruses: Multi-Faceted Therapeutics**
John Bell, PhD, Senior Scientist, Innovative Cancer Therapeutics, Ottawa Hospital Research Institute
Oncolytic viruses are much more than tumour lysing therapeutics. They can be engineered to selectively deliver to the tumour microenvironment therapeutic payloads. Examples of how we have engineered a tumour selective vaccinia virus for use as replicating
gene therapy vector will be presented.
9:05 Antibody-Drug Conjugate and Oncolytic Virus-Based IO Combinations: Different Modalities – Common Themes**
Philipp Müller, PhD, Senior Principal Scientist, Cancer Immunology & Immune Modulation, Boehringer Ingelheim Pharma GmbH & Co. KG
Despite the clinical breakthroughs achieved with checkpoint blockade, the overall proportion of patients experiencing durable responses remains relatively small. Therefore, the real promise for most cancer patients lies in complementary combination
therapies, combining checkpoint blockade with the immune-promoting/supporting properties of other therapeutic modalities, which help breach physical barriers, overcome immunosuppression and improve immune cell infiltration in tumors. This talk
will compare and highlight two of the latter categories: Antibody-drug conjugates and oncolytic viruses.
9:35 Attend Concurrent Track
10:05 Coffee Break in the Exhibit Hall with Poster Viewing
10:15 Speed Networking in the Exhibit Hall
10:45 Chairperson’s Remarks
To be Announced
Tina J. Hieken, MD, Professor of Surgery, Mayo Clinic
10:50 Determining the Selection of Combinatorial Therapies in Immune Oncology
Franco
Marincola, MD, CSO, Refuge Biotechnologies
Anti-cancer immunotherapy is dependent upon a pre-existent dialogue between cancer and immune cells in “immune infiltrated” tumors. In “immune silent” and “immune-excluded” tumors, this dialogue does not occur.
Analysis of the tumor microenvironment can dissect the biology underlying cancer immune responsiveness understanding mechanisms of action of therapeutics and documenting strategies adopted by tumor cells to escape immune recognition. This presentation
discusses the current understanding of the determinism of cancer resistance.
11:20 Neoadjuvant Immunotherapy for Melanoma**
Tina J. Hieken, MD, Professor of Surgery, Mayo Clinic
With efficacious new systemic therapies for advanced melanoma and new approvals for adjuvant treatment of resected high-risk stage III melanoma, the next logical step is exploring systemic therapy prior to surgical treatment for resectable high-risk
disease. Data from pilot clinical trials suggests that neoadjuvant immunotherapy might be a better approach to augment immunity than adjuvant therapy and that combinatorial regimens might enhance treatment response and improve patient outcomes,
but these approaches remain largely untested. In parallel, systematic study of drivers of response and toxicity are an active area of investigation.
11:50 Developing Personalized Neoantigen Cancer Vaccines to Target Solid Tumors**
Karoline Schjetne, PhD, Vice President Scientific Affairs, Vaccibody
Vaccibody is a clinical-stage biotech company dedicated to the discovery and development of novel immunotherapies. Vaccibody is a leader in the rapidly developing field of individualized cancer neoantigen vaccines and is using the Vaccibody technology
to generate best-in-class therapeutics to treat cancers with a high unmet medical need. The talk will focus on preclinical data underlining the superior vaccine technology and present clinical updates on the Phase I/IIa VB10.NEO vaccine trial
VB N-01.
12:20 Networking Lunch in the Exhibit Hall with Poster Viewing
13:05 NEW: Chairperson’s Remarks
Mathieu Cinier, PhD, Scientific Director, Affilogic
13:10 NEW: Managing T Cell Activation and Macrophage Differentiation with a Dual Player Nanofitin to Treat Cancer
Mathieu Cinier, PhD, Scientific Director, Affilogic
Success of immune checkpoint inhibitors highly depends of the number of T cell infiltrates as well as other factors such as inflammatory markers (e.g. Macrophage differentiation). We demonstrated the efficacy of a combination targeting several immunology pathways to treat cancer.
13:40 Combination Immunotherapy: The New Paradigm for the Treatment of Metastatic Melanoma and Renal Cell Carcinomay
John Wagstaff, MD, MB ChB, Director, South West Wales Cancer Institute & Professor, Medical Oncology, Swansea University College of Medicine
Both melanoma and renal cell carcinoma (RCC) has been increasing incidence over the past twenty years. When metastatic disease develops these cancers were notorious for their lack of response to conventional chemotherapy and the prognosis of these
patients was poor. The median survivals were between 11 and 13 months. The discovery of anti-CTLA4 (ipilimumab (Ipi)) and anti-PD1 (nivolumab (Nivo)) inhibitory monoclonal antibodies has transformed the prognosis of these patients. The five-year
survival of patients with metastatic melanoma is 53% and the survival curve is flat suggesting that these patients may be cured. In RCC the median survival with sunitinib was 26.1 months but the median OS for Ipi+Nivo has not been reached. These
impressive results do however come at the cost of autoimmune-related adverse events but despite this quality of life improves with these new therapies. these therapies herald a new era in the treatment of metastatic cancers.
14:10 Ator-1015 – From Discovery to the Clinic
Anne Mansson-Kvarnhammar, PhD, Senior Scientist, Alligator Bioscience AB
ATOR-1015 is a tumor-directed CTLA-4 x OX40 bispecific antibody designed to improve the efficacy and safety of current CTLA-4 targeting therapies. This talk will cover preclinical in vitro and in vivo data and give an overview of the ongoing Phase I study and the clinical development path.
14:40 Close of Summit
**Presentations delivered via a live, interactive video conferencing platform.**
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