The future of immuno-oncology drug development is positioned in combination therapies, where immunotherapy modalities are tested in rational combinations with other immunotherapies or targeted therapies for synergistic effects. Combination immunotherapy
promises to deliver long-term survival benefits that may be unavailable with current approaches. The Inaugural Combination Immunotherapy meeting, part of the Second Annual Immuno-Oncology Summit Europe,
will explore the most effective combinations of immunotherapy with chemotherapy, other immunotherapy or targeted therapy. Coverage will include understanding the mechanism of action, managing toxicity, strategies to design synergistic combinations,
biomarker development and case studies of ongoing combination immunotherapy studies from the leading researchers in industry and academia.
Thursday, 23 March
07:45 Registration and Morning Coffee
09:00 Chairperson’s Opening Remarks
Tom Lillie, M.D., Ph.D., Vice President and Head, European Clinical Development, Merck Sharp & Dohme
09:05 Re-Exploring the Framework of Combination Therapies in Oncology
Tom Lillie, M.D., Ph.D., Vice President and Head, European Clinical Development, Merck Sharp & Dohme
An enduring dream in oncology has been to utilize the innate value of the immune system to battle cancer. In recent years, there have been numerous advances in this arena and one such extraordinary development has been the rise of checkpoint inhibitors.
Among the immunotherapies, pembrolizumab (anti-PD-1) has shown promise with ‘rational’ combinations (e.g. immune/targeted agents) and ‘less rational’ combinations (e.g. chemo/radiotherapies) in multiple oncology indications,
including non-small cell lung cancer, advanced melanoma and certain types of head and neck cancer.
09:35 Opportunities and Challenges in the Combination Immunotherapy of Cancer
Jon Wigginton, M.D., Senior Vice President, Clinical Development & CMO, MacroGenics
There has been tremendous progress in the field of cancer immunotherapy as it has moved recently into the mainstream for the treatment of many cancers. A broad range of non-clinical studies, and more recently, powerful new clinical data from studies
combining anti-PD-1 (nivolumab) and anti-CTLA-4 (ipilimumab) for the treatment of patients with melanoma, have focused considerable attention on the potential promise of combination cancer immunotherapy. This presentation will provide an overview
of current progress, lessons learned, and future prospects for the combination immunotherapy of cancer.
10:05 Using Genomics to Predict Effective Combination Immunotherapy
Christian Ottensmeier, M.D., Ph.D., Professor, Experimental Cancer
Medicine, University of Southampton
Cancer immunotherapy is the key major advance in oncology and has taken its place in routine management of solid cancers. Still, only a minority of patients benefit. With the explosion of treatment options, it is becoming critically important
to make rational choices about treatment combinations. In this presentation, we will explore how molecular analytics might be used to inform treatment choices to achieve this aim.
10:35 Coffee Break in the Exhibit Hall with Poster Viewing
11:15 PD-1 Antibody, a Broad Spectrum Antineoplastic Therapy, Has the Potential to Be Foundational as a Monotherapy and in Combination Therapy for the Cancer Patient
Roy D. Baynes, M.D., Ph.D., Senior Vice President and Head, Global Clinical Development, CMO, Merck
Sharp & Dohme
PD-1 antibody has, as monotherapy, shown broad spectrum activity across a large number of cancer types and has already been demonstrated to improve survival in malignant melanoma and non-small cell lung cancer, across lines of treatment, compared
with standard of care. A number of combinations with PD-1 antibody are now showing major promise. Precision medicine optimizes treatment decisions in certain tumor types. Recent clinical data will be presented.
11:45 Combined Ipilimumab and Anti-PD-1 Antibody Therapy – Questions on Sequencing and Dosing
Lucie Heinzerling, M.D., Ph.D., MPH, Head of Dermatooncology, University Hospital
While full-dose ipilimumab in combination with the anti-PD-1 antibody nivolumab was clearly efficacious in metastatic melanoma and led to approval of the treatment scheme, toxicity was considerable with 56% grade 3/4 side effects. Thus, low-dose
ipilimumab combined with anti-PD-1 is investigated as well as sequential single-agent checkpoint treatment followed by the combination. While comparative studies are missing, available data on dosing and sequencing is analyzed to facilitate
clinical decision making.
12:15 Synergy of Immune Modulators in Cancer Management
Angus Dalgleish, M.D., Professor, Oncology, St. George’s University of London
This presentation will cover: 1) the resurrection of thalidomide and the development of analogues, notably Revlimid (lenalidomide) and pomalidomide in the treatment of myeloma and lymphomas and their potential role for solid tumours, 2) a
review of the reason why so many cancer vaccine trials have failed and the reason that positive results are beginning to be seen with this strategy when added to other modalities, 3) the role of many other drugs which favourably modulate
the immune system when used in low doses. These include: gemcitabine, cyclophosphamide, paclitaxel, naltrexone, artusenate and the cannabinoids.
12:45 Luncheon Presentation: A Novel Phenotypic Platform for Predicting Tumor Immune Response
Mark Paris, Ph.D., Technical Liaison, Mitra Biotech
13:45 Dessert Break in the Exhibit Hall with Poster Viewing
14:15 Chairperson’s Remarks
Lindy Durrant, Ph.D., Professor, Cancer Immunotherapy, University of Nottingham; Joint CEO & CSO, Scancell
14:20 Combinations of Novel Vaccines with Checkpoint Inhibitors
Lindy Durrant, Ph.D., Professor, Cancer Immunotherapy, University of Nottingham; Joint
CEO & CSO, Scancell
We have two cancer immunotherapy platforms. ImmunoBody utilises both cross- and direct-presentation to increase T-cell avidity by 100 fold. In Phase I trials, it induced T-cell responses, tumour regression and long term survival. In combination
with checkpoint inhibitors, it induced 100% tumour regression in established models. Phase II trials in combination with checkpoint inhibitors are planned. Moditope stimulates powerful anti-tumour T-cell responses against neo-epitopes
produced by enzymes induced by cellular stress.
14:50 Immunomodulating Antibodies Synergize with Cancer Vaccine Approaches
Andrea van Elsas, Ph.D., CSO, Aduro Biotech Europe
This talk will address the synergistic potential of cancer vaccines and immune checkpoint inhibitors as well as other immunomodulators for the treatment of cancer.
15:20 Refreshment Break in the Exhibit Hall with Poster Viewing
16:00 Intravenous Delivery of Oncolytic Virus to Tumours in Patients Immunologically Primes Tumours for Sequential Checkpoint Blockade
Alan Melcher, M.D., Ph.D., Professor, Translational Immunotherapy, The Institute of Cancer
Oncolytic viruses (OV) act significantly by stimulating anti-tumour immunity. We have focused on systemic delivery of OV and shown in patients that intravenous reovirus accesses tumours in both the liver and brain in patients. Moreover,
infection upregulates interferon-regulated gene expression within patient-treated tumours, immunologically ‘priming’ tumours for sequential immune checkpoint blockade, such that addition of anti-PD-1 blockade to intravenous
reovirus enhances systemic therapy in preclinical models.
16:30 Combination of Local Tumor Treatment with Ipilimumab in Patients with Malignant Melanoma
Sebastian Theurich, M.D., Lecturer, Internal Medicine, Hematology and Oncology, University Hospital Cologne, Germany
The therapeutic strategy of immune checkpoint inhibition has revolutionized cancer immunotherapy and significantly improved outcomes of patients with advanced melanoma and other cancers. A fraction of patients achieves long-term remissions
suggesting profound immune control. Current research focuses on strategies to improve such enduring remissions and, among others, local radiotherapy is a promising option via the induction of immunogenic cell death and other mechanisms,
which in the sum enhance systemic tumor-specific immune responses.
17:00 End of Day
Friday, 24 March
08:00 Morning Coffee
08:30 Chairperson’s Remarks
David Feltquate, M.D., Ph.D., Vice President, Oncology Development, Bristol-Myers Squibb
08:35 Challenges in IO-IO Combination Dose Finding: A Case Study of Ipilimumab/Nivolumab in NSCLC
David Feltquate, M.D., Ph.D., Vice President, Oncology Development, Bristol-Myers
Development of IO-IO combinations will be important to further enhance the magnitude and scope of clinical activity of IO therapies. In this talk, I will review the development of an ipilimumab/nivolumab combination therapy and discuss
the challenges with particular emphasis on NSCLC as a case study.
09:05 Challenges in Developing Immunotherapy Combinations
Maria Karasarides, Ph.D., Senior Director, Immuno-Oncology, Global
Medicines Development, AstraZeneca
This presentation will cover the pros and cons of choosing a specific trial design, caveats in selecting a combination dose, what is a positive efficacy signal, and difficulties in prioritizing combinations during development.
09:35 Combinations of Novel Agents with PD-1/PD-L1 Checkpoint Inhibition in Early Phase Trials
Stefan Symeonides, Ph.D., Senior Lecturer, Experimental Cancer
Medicine, Edinburgh Cancer Research Centre, University of Edinburgh
The recent wealth of exciting data for cancer immunotherapies, and especially combinations, creates a fortunate but complicated situation: how to now explore all these rapidly growing options in the clinic. Efficient trial designs
and early exploration of clinical and biological activity are essential, as are prioritising translational analyses to help us refine, optimise and compare treatments. Illustrations will be provided from our current early phase
trials, focusing on combinations of novel agents with PD-1/PD-L1 checkpoint inhibition.
10:05 Networking Coffee Break
10:35 T Cell Function in Cancer, Promoted by Single Agents and Combination Therapies
Daniel E. Speiser, M.D., Professor, Clinical Tumor Biology & Immunotherapy,
Department of Oncology, University of Lausanne
The recent remarkable progress of immunotherapy in patients with solid cancers is based on anti-cancer T cells and their potential to destroy tumors. Physiologically, these T cells are under tight control of several cellular and
molecular regulatory circuits, consisting of activatory and inhibitory cells and signal cascades. Intense research allows increased understanding of T cell regulation in cancer patients, guiding the design of innovative clinical
trials and further therapy improvements.
11:05 Towards the Rational Design of Combinatorial Immunotherapy – The Need for Tissue-Based Biomarkers
Ioannis Karydis, D.Phil., MRCP, Associate Professor, Oncology, Cancer Sciences Unit, University of Southampton
Choosing the correct treatment regimen becomes more complicated with every new cancer immunotherapy agent. Clinical trial costs and a limited pool of patients prevent us from testing every combination across a range of indications.
By employing a rational clinical trial design approach utilising tissue-based predictive biomarkers and a better understanding of underlying molecular mechanisms, we can optimise resource use and determine the target populations
most likely to benefit.
11:35 Combinatorial Immunotherapy Approaches in Ovarian Cancer
Lana Kandalaft, Pharm.D., Ph.D., Assistant Professor & Director, Center
for Experimental Therapeutics, Department of Oncology, University of Lausanne; Tenure Track Assistant Professor, Ludwig Cancer Research Lausanne Branch
The presence of T cells in the ovarian cancer tumor microenvironment is correlated with improved progression-free and overall survival, while the presence of regulatory T cells and expression of T cell inhibitory molecules is correlated
with a poor prognosis. This finding indicates that immunotherapy could hold promise in improving the treatment of ovarian cancer, but it also classifies ovarian cancer patients into two subtypes: the immunogenic and the non-immunogenic.
In this talk, combinatorial approaches of immunotherapy will be described for each subtype highlighting current results with personalised cancer vaccines and immunomodulatory agents and summarising the immune effects of selected
chemotherapeutic and radiotherapeutic agents when used in combination.
12:05 End of Conference