Cambridge Healthtech Institute’s 4th Annual

Combination Immunotherapy

Distinguishing Promising Cancer Immunotherapy Combinations from the Crowd

20-21 March 2019

 

Treating cancer patients with an immunological combination is an essential strategy that is still growing in popularity. With so many trials ongoing though, it can all get a bit confusing. There are many factors that may influence therapeutic success, including but not limited to double immunotherapy combinations or immune checkpoint inhibitors combined with conventional cancer therapy. Predictive biomarkers, novel antigens, therapeutic mechanism, reducing toxicity and the immune response are all important considerations. This and more will be discussed in at the Combination Immunotherapy conference.

Final Agenda

WEDNESDAY 20 MARCH

ANTIBODY AND CHECKPOINT INHIBITOR COMBINATIONS

7:45 Registration and Morning Coffee

8:30 Chairperson’s Opening Remarks

Daniel S. Chen, MD, PhD, Chief Medical Officer, IGM Biosciences


8:35 FEATURED PRESENTATION: Engineering Therapeutics and the Future of Cancer Immunotherapy

Daniel S. Chen, MD, PhD, Chief Medical Officer, IGM Biosciences

Single agent and combination cancer immunotherapy with PD-L1/PD-1 inhibitors have generated durable responses in a subset of patients and a survival benefit in a broad group of patients suffering from terminal cancers. However, the next generation of cancer immunotherapeutics have not yet led to a similar therapeutic impact, potentially supporting the complexity and highly regulated nature of the human immune system. However, advances in engineered therapeutics, from cellular therapy to highly modified multispecifc molecules, are enabling novel methods to modulating biology and the immune system to eradicate cancer.

9:05 KEYNOTE PRESENTATION: PD-1 Antibodies Are Transforming Cancer Therapy Both as Mono- and Combination Therapies

Roy D. Baynes, MD, PhD, Senior Vice President and Head, Global Clinical Development, CMO, Merck Sharpe & Dohme

PD-1 antibodies have shown significant activity across more than 25 major cancer types. PD-1 antibody activity in monotherapy may be enriched with precision medicine tools. Precision medicine may help define resistance biology and enable rational combinations. Certain combinations (e.g. chemotherapy + PD-1 antibodies) may be broadly active without regard for biomarker-based selection.

9:35 Sponsored Presentation (Opportunity Available)

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

ANTIBODY AND CHECKPOINT INHIBITOR COMBINATIONS (CONT.)

10:45 IgA as an Alternative Isotype to Treat Cancer, and Combination with Innate Checkpoint Inhibition

Jeanette Leusen, PhD, Associate Professor, Laboratory for Translational Immunology, Immunotherapy Group, University Medical Center Utrecht

All clinically used mAbs are of the IgG class but IgA can be very effective in vitro and in vivo, with a distinct mechanism of action: IgA has the unique capacity to activate neutrophils, our most abundant but often underappreciated white blood cell. For a long time, it was hard to produce and purify enough IgA for preclinical experiments. Furthermore, IgA has a short half-life and mice lack the IgA receptor which hampers the preclinical research. In the presentation these issues will be addressed and answered, with preclinical examples for lymphoma and neuroblastoma.

11:15 Bispecific Antibodies for Tumor-Directed Blockade of CD47, a Ubiquitously Expressed Immune Checkpoint

Krzysztof Masternak, PhD, Head of Biology, Research, Novimmune SA

To evade the immune system, cancer cells overexpress CD47, a ubiquitous innate immune checkpoint. Bispecific antibodies afford selective tumor-directed CD47 targeting, allowing for an improvement of therapeutic window as compared to monospecific strategies, such as anti-CD47 mAbs and SIRP alpha-Fc fusion proteins. In vivo translational studies demonstrate that tumor-directed blockade of CD47 with bispecific antibodies results in enhanced anti-tumor activity and a modification of the properties of the tumor microenvironment.

11:45 The Use of Bispecific Antibodies to Modulate Anti-Tumour Immune Responses

Neil Brewis, PhD, DSc, CSO, Research and Development, F-star

mAb² ™ is a bispecific antibody format that allows a “plug and play” modular strategy F-star product strategy to address heterogeneity of tumour phenotypes in vitro and in vivo efficacy of F-star bispecific antibodies targeting oncology pathways.

12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:45 Dessert Break in the Exhibit Hall with Poster Viewing

13:15 Session Break

MULTIPLE IMMUNOTHERAPY COMBINATIONS

14:00 Chairperson’s Remarks

Johan Lantto, PhD, Project Director, Immuno-Oncology, Symphogen

14:05 On the Requirement to Induce Immune Modulation Prior to Checkpoint Inhibitor Therapy: Lessons from Mice and Men

Angus Dalgleish, MD, FRCP, FRACP, FRCPath, FMedSci, Foundation Professor of Oncology SGUL, Principal of the Institute of Cancer Vaccines and Immunotherapy, Institute of Infection and Immunity, St George’s University of London

Checkpoint inhibitors (CPIs) have revolutionized the treatment of several cancer types, however, the majority of patients do not benefit on single agent CPIs. Mouse studies show that response to CPIs do not occur unless innate immune cells are activated and other markers are reduced. IMM-101 activates innate immune responses and has been reported to enhance clinical responses to CPIs in melanoma patients.

14:35 Regulatory Challenges and Opportunities for Combination Development

Elena Spanjaard, PhD, Global Head of Regulatory Affairs, Regulatory Affairs, Celyad

Efficient co-development of novel combination therapies presents complex regulatory challenges. Regulatory guidelines provide a framework for development of investigational agents that are intended for use in combination. Key considerations for selecting combination agents and modality-specific considerations will be highlighted. Current special regulatory designations and expedited pathways will be reviewed, including qualifying criteria, features, and benefits.


15:05 Problem Solving Roundtable Discussions

Why Are IO-Combination Therapies Harder to Develop than Anticipated?

Moderator: Alexander Eggermont, MD, PhD, Professor Surgical Oncology, University Paris-Sud; Director General, Direction, Gustave Roussy Comprehensive Cancer Center

Optimal Checkpoint Combinations

Moderator: Angus Dalgleish, MD, FRCP, FRACP, FRCPath, FMedSci, Foundation Professor of Oncology SGUL, Principal of the Institute of Cancer Vaccines and Immunotherapy, Institute of Infection and Immunity, St George’s University of London

 

16:05 Refreshment Break in the Exhibit Hall with Poster Viewing

16:35 Lessons from Melanoma and the Development of Combination Immunotherapies

Alexander Eggermont, MD, PhD, Professor Surgical Oncology, University Paris-Sud; Director General, Direction, Gustave Roussy Comprehensive Cancer Center

The immune checkpoint inhibitors (ICIs) anti-CTLA-4 (Cytotoxic T Lymphocyte Antigen-4) and anti-PD1/anti-PDL1 (programmed death-1 receptor and its ligand PD-L1) are the basis of an unprecedented development of successful immunotherapies across many tumor types. Melanoma has been at the frontier of this development where within 7 years, advanced melanoma was transformed into a curable disease in over 50% of patients.

17:05 Discovery and Development of Antibody Combinations for Cancer Immunotherapy

Johan Lantto, PhD, Project Director, Immuno-Oncology, Symphogen

Immune checkpoint blockade using monoclonal antibodies targeting CTLA-4 and the PD-1/PD-L1 axis has shown impressive efficacy in the treatment of various cancers. However, since only a subset of the patients responds to these therapies, search for other relevant targets, and development of more powerful therapeutic combinations has become an intense area of focus. Here, we present Symphogen’s approach to discovery and development of potent antibody combinations for cancer immunotherapy.

17:35 Safety Issues in Combinatorial Immunotherapy Trial Design

Ioannis Karydis, BM, BCh, MA, DPhil, MRCP, Associate Professor in Medical Oncology, Cancer Sciences, University of Southampton

The last decade has seen a rapid paradigm shift in clinical trial design; a number of innovative approaches have accelerated the process of bringing a novel agent from lab to clinic. Development of immunooncology agents has benefited from these, however the unique characteristics of these agents pose specific challenges when it comes to determining their safety profile. This talk will summarise the issues at play and present ways to address them.

18:05 Networking Reception in the Exhibit Hall with Poster Viewing

19:05 Close of Day

THURSDAY 21 MARCH

NOVEL IMMUNOTHERAPY COMBINATIONS

8:00 Morning Coffee

8:30 Chairperson’s Opening Remarks

Graham Pockley, PhD, CEO, multimmune GmbH; Professor of Immunobiology, John van Geest Cancer Research Centre, Nottingham Trent University

8:35 NK Cell-Based Therapy for the Treatment of Tumours Expressing Membrane Hsp70

Graham Pockley, PhD, CEO, multimmune GmbH; Professor of Immunobiology, John van Geest Cancer Research Centre, Nottingham Trent University

Despite progress, significant numbers of individuals continue to die of aggressive, therapy-resistant disease. Professor Pockley will introduce a new natural killer (NK) cell-based approach for the treatment of aggressive cancers which express a membrane form of Hsp70 – ‘one drug could indeed fit all’.

9:05 Novel RNA-Transfected Dendritic Cells as a Universal Vaccine Platform to Induce T Cells Recognizing Shared Antigens as well as Mutated and Non-Mutated Neoantigens

Gerold Schuler, PhD, MD, Head of Department, Dermatology, University Hospital Erlangen

Our novel NFKB-activated RNA-transfected dendritic cells (DCs) induce effector and memory T cells, and also stimulate NK cells for innate immune attack. A unique advantage is that we can not only load these DCs with shared or mutated antigens but via transfection with total tumor mRNA also arm the DC with non-mutated neo-antigens including cryptic peptides. This exceptional vaccine platform has recently produced convincing clinical benefit in various tumor entities.

9:35 Sponsored Presentation (Opportunity Available)

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

10:45 The Exercise of Taming the Immune System

Per Thor Straten, PhD, Professor, Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev

We have characterized a novel co-stimulatory pathway in CD8 T cells. The stimulatory signal goes via activation induced surface expression of both the receptor as well as the soluble ligand. Importantly, increased signaling via this pathway leads to increased cytokine release and proliferation, whereas blocking of the pathways by monoclonal antibody or siRNA technology leads to diminished production of TNF-α and INF-γ, as well as and reduced proliferation.

11:15 Macrophages: Immunosuppressive Cells in the Tumour Microenvironment

Jeffrey Pollard, PhD, Professor, University of Edinburgh

11:45 Rational Immuno-Oncology (IO) Combination Therapy

Wilkinson_RobertRobert Wilkinson, PhD, Director of Oncology Research, MedImmune Ltd, Cambridge UK

Immuno-Oncology (IO) therapy, such as immune checkpoint blockade antibodies, has created a paradigm shift in the treatment of some cancers. Our understanding around biomarkers of which patients will benefit from IO therapy continues to evolve; alongside how best to modulate the anti-cancer immune response through rational/data driven combinations with other IO therapies (targeting innate and/or adaptive immune cells), targeted therapies and/or standard of care treatments, such as chemo- and radio-therapy.

12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:45 Dessert Break in the Exhibit Hall with Poster Viewing

13:30 Close of Combination Immunotherapy