Co-Chair’s Opening Remarks
Preclinical Mechanistic Combinations Plenary Session
IO Combinations with CAR-T Therapies
Preclinical Data on BiTE Platform and Associated Combinations
Julie Bailis, PhD
Principal Scientist, Oncology Research, Amgen, Inc
The Tumor Explant Model as a Model System to Understand Treatment Effects
This talk will look at the infiltration of lymphocytes and cytokine/ chemokine profiles into the tumor and which drugs/drug combinations can drive that through a tumor explant model. This fully human, fully immunocompetent model system allows to monitor and understand the immediate effects of systemic treatments on the tumor and surrounding normal tissue. This model to is used to identify mechanisms of response and resistance in tumor types.
Model Systems for Studying Combinations
Single Cell Sequencing and Mechanisms of Immuno-Resistance
Prioritizing Combinations using a Human Phenotypic Model for Drug Development
Panel Discussion: Predicting IO Combination Success
Predicting IO combination success does not have to wait until phase 3. This panel will address how do we predict what is going to work and what is not going to work by looking at model systems and early translational clinical trials.
Translational Science & Emerging Biomarkers Plenary Session
The Role of the Gut Microbiome in Response to Immunotherapy
Major progress has been made in the treatment of cancer through the use of immunotherapy, however not all patients respond and new insights into mechanisms of response and resistance are critically needed. We studied the microbiome in patients with metastatic melanoma going onto immune checkpoint blockade, and demonstrated that responders to therapy had a higher diversity of the gut microbiome and compositional differences compared to non-responders. Importantly, this was associated with differences in anti-tumor immunity. Based on this and other data, efforts are ongoing to modulate the microbiome to enhance responses to immunotherapy – however complexities exist and will be discussed in this talk.
IO Combinations Based on Tumor Mutation Analysis
Demystifying Tumor Immunogenomics: Key Challenges and Solutions
Advances in immuno-oncology research have led to promising results with NGS-guided analysis for sensitive neoantigen identification as well as for the discovery of novel biomarkers. However, standard approaches suffer from limitations. Personalis addresses these issues using its proprietary ACE ImmunoID platform, which combines augmented exome and transcriptome sequencing with advanced analytics. We’ll share data that demonstrates the technical characteristics with an overview of the analytical validation, bioinformatics pipeline, neoantigen prediction and immunogenomics reporting capabilities. Additionally, we will be sharing a case study demonstrating ACE ImmunoID’s further utility in biomarker discovery through identifying methods of tumor escape in patients treated with checkpoint modulators.
Predictive Biomarkers of Clinical Response Reveal Synergy Mechanisms Between Combination Immunotherapies Using Single Cell Proteomics
In this talk, Sean Mackay, Co-Founder and CEO, IsoPlexis will provide data that demonstrates how:
- Polyfunctional Strength (the secretion of two more cytokines per cell, where the cytokine secretion intensity is tied to the cell which produced it) is a more accurate predictor of clinical outcome than flow cytometry, bulk protein analysis or gene array
- Single Cell Functionality has correlated with Objective Response across IO: CAR-T with Kite Pharma, Checkpoint Inhibitors and Cancer Vaccines
- Polyfunctionality of CD4+ T-cells is a predictor of Overall Survival of patients treated with the GVAX Vaccine where post- versus pre-vaccination fold-change of the polyfunctional strength index associated with patient overall survival (P = 0.001).
TCR Sequencing as a Predictive Biomarker of Response in IO
Operationalizing Combinations Plenary
Collaborations that Drive Combination Activities: The Science and Operations
In this session, Merck clinical operation leaders address the operational considerations of combination studies. This includes:
- What it takes to run combination studies from an operational standpoint
- Creating drug sourcing activities, safety and quality agreements and with partnering pharma companies
- Managing startup activities such as investigator brochures, risk language around combinations and a managing the safety along the way
- Addressing drug procurement aspects and maintaining those quality aspects of bringing the combinations to the studies
Novel Platform Trial Design
Novel-novel combinations platform trials offer the opportunity to efficiently evaluate and screen out for important new therapies in a standing clinical trials infrastructure. They also offer other efficiencies by use of statistical modeling to formally leverage both historical information and concurrent information in related populations. This talk will describe the various operational and statistical aspects of platform trials for novel-novel combinations in oncology.
Regulatory Framework for Investigating & Approving Combinations
This talk will focus on the FDA guideline on novel-novel combinations and its application including existing approvals and future expectations.
Biomarker Procurement for IO Combinations
The operational challenge that people still have regarding biomarkers is determining how you get material from patients that you can do analysis on and how do you standardize this? How do we get the biomarker questions answered that are at the heart of making combinations work?
Panel Discussion: The Operational Challenges of IO Combination Trials
The complexities of doing combination clinical trials are huge. This panel will address:
- How do you do clinical trials with different companies products?
- How do you coordinate the supply chain with 2 drugs?
- Who controls the rights? System processes? What are the thresholds?
IO Emerging Technologies & Innovative Solutions
- 6:15 pm
This plenary will showcase companies that have technologies and solutions that will help stakeholders in the IO field advance combination developments to provide treatment for cancer patients.
Co-Chair’s Opening Remarks
Emerging Clinical Combinations Plenary Session
PD-1 Antibody Based Immuno-oncology Novel Combinations Across Indications
After establishing PD-1 antibody monotherapy activity, enabled by precision medicine, across multiple cancer types and lines of treatments study of combination therapies across multiple indications is suggesting significant promise. The data thus far suggest the PD-1 antibody is both broad spectrum across tumors and foundational to the combination approach. Novel combinations include those with standard therapies (e.g. chemotherapy), with targeted therapies, with other immune modulators and with tumor vaccines or oncolytic viruses.
Immunotherapy Combinations with PARP Inhibitors
Overcoming the Resistance to Immune Checkpoint inhibitors via Rational Combination of Immunotherapy
- Preclinical studies to provide rationale for the combination Immunotherapy
- Design and develop science-driven clinical studies of combination Immunotherapy
- Biomarker analysis on the specimens from clinical trials of combination Immunotherapy
IDO Inhibition Combination Trial Perspectives: Epacadostat + Pembrolizumab for Melanoma
This talk will consist of two parts. In part one, Incyte will share the clinical data and full analysis on pembrolizumab in combination with epacadostat for Melanoma. In part two, Dr Jason Luke, University of Chicago, will address the mechanisms of why people thought it should work, why it has not and what can be learned moving forward. There will be 10 minutes at the end of the 2-part talk for Q&A.
Update on CD40 Cancer Therapeutics
Emerging Data Combinations in Clinical Trials Plenary Session
Novel Approaches to Engineered Cancer Immunotherapy
In 2018, advances in therapeutic technologies are changing the options available for cancer immunotherapy. From engineered large molecules, to protein modification techniques, from cellular immunotherapy to personalized cancer vaccines, how we approach therapeutics is broader than ever. Objectives for engineered cancer immunotherapy approaches, techniques and emerging clinical data will be presented.
Lymphocytes as a Drug for the Treatment of Metastatic Cancer
In this talk, Dr Steven Rosenberg, Chief, Surgery Branch at the National Cancer Institute, will discuss cancer immunotherapy using the adoptive cell transfer of autologous lymphocytes with antitumor activity with an emphasis on the identification of T-cells that recognize the products of mutations unique to the individual patient’s cancer.
Panel Discussion: Scalability of T-Cell Therapy
This panel will discuss the clinical challenges with IO combinations and ways to move forward. Talking points include:
- What is the scalability of T-cell therapy?
- How do we scale T-cell therapy and what are the plans for getting the therapy into all the patients who need it?
- How are we going to scale neo-antigen specific therapy if this is going to be novel to each patient?
- How do we deal with resistance to T-cell therapies?
- When should patients get TILs vs when they should get other therapies?
- Do we need to alter the microenvironment to maximize these therapies?
- What combination therapy should be given with T-cell therapy?
- Will T-cell therapy lead to epitope spreading?
Business Aspects Plenary Session
Executive Fireside Chat: Partnership Deals and Combination Strategies
Pharma and biotech executives come together on this fireside chat to share the nature of their partnership. They will address the partnership journey from the very start, what it encompassed and how it has evolved.
Panel: IO Combination Deals and Partnerships
- What is the nature/landscape of the deals being done in combinations? (IO and non IO)
- Who is doing them, what are they like, and are there any changes in the nature of the dealmaking that is occurring within IO because of the need for combinations?
- Are the recent failures changing the nature of the partnering relationships? Is that changing the way people are thinking when it comes to funding at the early stage?
- What is shaping the evolving nature or actual deal terms from the spectrum of collaboration through licensing to full sharing between biotech and pharma?
Additional Panelists TBD
Panel: Investment Strategies Driving IO Combinations
- What are the types of investments that will enable combinations? (ie: early mechanisms and novel platforms; pharma/biotech partnerships)
- From an investment perspective, how do you identify what is coming up the pipeline? With all the combination studies out there, how do you get behind the right combination?
- How do investors make the decision to invest in a seed round, series A of a novel mechanism or platform that is more likely to be useful in combination, or licensing assets?
- Are we emphasizing too much on the adaptive immune system or should we look at innate immune system?
Additional Panelists TBD
Panel: Assessing Value & Market Access Implications of Immuno-Oncology Combination Therapies
- How do we think about the value?
- How is the IO market access landscape evolving?
- Where are we now in terms of payer management?
- What is the impact of reimbursement challenges?
- What does the future payer initiatives look like?
- What pricing strategies/reimbursement models are there to help address the issues?
- What can we demonstrate and communicate value to payers for optimal reimbursement/market access?
End of Conference