Cambridge Healthtech Institute’s 7th Annual
Combination Cancer Immunotherapy
Rational Combination Strategies to Improve Efficacy and Reduce Resistance
August 5-6, 2019
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 Seventh Annual Combination Cancer Immunotherapy conference will explore the most effective combinations of immunotherapy
with conventional cancer therapy, with other immunotherapy or with 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.
Final Agenda
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MONDAY, AUGUST 5
7:30 am Registration Open and Morning Coffee
8:25 Chairperson’s Opening Remarks
Rakesh Dixit, PhD, DABT, President & CEO, Bionavigen
8:30 KEYNOTE PRESENTATION: Immunotherapy Combinations: Challenges and Opportunities
Rakesh Dixit, PhD, DABT, President & CEO, Bionavigen
Immunotherapy, incorporating immune checkpoint inhibitors (ICI), has revolutionized the treatment of many deadly cancers for many cancer patients in the last decade. But the majority of the cancer patients have not reaped the benefits of the current immunotherapy
agents because of the tumor-induced immune suppression and intrinsic aging-related weakened immune system. Of nearly 2,000 or more immunotherapy-centric combination trials, the combinations of ICIs with chemotherapy, radiation, NK cell antagonists,
cytokines, cancer vaccines, oncolytic viruses, etc., have shown some ability to transform cold tumors into hot tumors with impressive efficacy in some cancers. However, the challenges remain with regard to the selection, including the MOA-based combinations,
dosing, schedules, and personalized biomarkers for different tumor types. The presentation will provide a comprehensive overview of the immunotherapy combinations, patient selection and biomarker-based strategies to enhance the value of immunotherapy
combinations, including how to minimize toxicities and enhanced overall survival.
9:00 Next-Generation Immune Checkpoints – Deciphering Key Roles in the TME
Catherine Sabatos-Peyton, PhD, Director, Exploratory Immuno-Oncology, Novartis
The success of PD-1 pathway inhibitors has led to rapid expansion of clinical trials in immuno-oncology, including multiple trials exploring partner pathways to enhance responses and durability and to tackle nodes of resistance. Next-generation checkpoint
inhibitors including TIM-3 and LAG-3 have broad expression profiles, and preclinical research reveals novel and critical mechanisms of action for these pathways. Translational data from clinical trials also informs understanding of novel mechanisms.
9:30 Immunotherapy Combinations: Lessons Learned and Future Outlook
Maria Karasarides, PhD, Executive Director, Immuno-Oncology Global Development, Regeneron Pharmaceuticals
This presentation will cover: 1) biological mechanisms driving tumor susceptibility to ɑ-PD-1 based immunotherapy combinations, 2) learning from early phase clinical trials investigating ɑ-PD-1 based combination treatments, 3) strategies for achieving
maximal T cell responses with tumor antigen-directed immunotherapies, and 4) future outlook: turning roadblocks into insights.
10:00 Coffee Break
10:30 VSV-GP-Driven Immune Modulation and Therapeutic Combinations: Tackling the “Cold Tumor Space”
Philipp Müller, PhD, Principal Scientist, Cancer Immunology, Boehringer Ingelheim
Oncolytic viruses constitute a highly promising class of emerging anti-cancer therapeutics. VSV-GP, a very potent and rapidly replicating oncolytic virus, is capable of inducing strong anti-tumor immunity in “cold” tumors by increasing
immune cell infiltration/activation within infected tumors and creating a T-cell-inflamed tumor environment that empowers the immune system to control tumor growth. Therapeutic combinations with checkpoint inhibitors like α-PD1 or SMAC mimetics
further enhance the anti-tumor activity of VSV-GP.
11:00 Lifting the Veil: De-stealthing the Tumor with Combination Immunotherapy
Huabiao Chen, MD, PhD, Principal Investigator, Vaccine & Immunotherapy Center, Massachusetts General Hospital; Instructor, Medicine, Harvard Medical School
11:30 Q&A with the Speakers
12:00 pm Enjoy Lunch on Your Own
1:25 Chairperson’s Remarks
Rakesh Dixit, PhD, DABT, President & CEO, Bionavigen
1:30 Why Are We So Late in Treatment of Breast Cancer Using ICI?
Stefan
Glueck, MD, PhD, FRCPC, Professor of Medicine, Vice President, GMA Early Assets, Celgene Corporation
Positive studies have led to the US FDA approval of several immune checkpoint inhibitors but none to date are approved in breast cancer (BrCa). Moreover, PD-1/PDL-1, MSI high (and dMMR), MTB are the currently “best” predictive markers
for IO therapy. BrCa actually has some of these markers positive only in subsets and less frequently expressed than most other tumors, e.g. malignant melanoma or non-small cell lung cancer and others. To improve the potential efficacy of ICI in
breast cancer, the addition of chemotherapy was one of the strategies. A large RCT in breast cancer was reported at ESMO 2018 and more are underway. We will discuss the mechanism of action and its impact on BrCa.
2:00 KEYNOTE PRESENTATION: Cooperative Immune-Mediated Mechanisms of the HDAC Inhibitor Entinostat, an IL-15 Superagonist,
and a Therapeutic Cancer Vaccine
Sofia Gameiro, PharmD, PhD, Head, Immunomodulation Group, Laboratory of Tumor Immunology and Biology, NCI, NIH
Immunotherapy aimed at alleviating immunosuppression while promoting immune effector function may increase clinical responses for patients with solid carcinomas. Here, we demonstrate that the class I HDAC inhibitor entinostat enhances the anti-tumor
efficacy of an IL-15 superagonist plus vaccine in murine carcinoma models, by promoting antigen-specific responses, enhanced infiltration of activated CD8+ T cells with maximal granzyme B, reduction of Tregs in the tumor, and decreased expression
of the checkpoint VISTA on multiple immune subsets.
2:30 CX3CR1+CD8+ T Cells Are Responsible for the Clinical Benefit of Chemoimmunotherapy in Metastatic Melanoma Patients after Disease Progression on PD-1 Blockade
Yiyi Yan, MD, PhD,
Assistant Professor, Medicine and Oncology, Division of Medical Oncology, Mayo Clinic, Rochester, MN
In metastatic melanoma patients who have failed anti-PD-1 therapy, the chemo-immunotherapy combination showed favorable clinical outcomes and an acceptable toxicity profile. CX3CR1+ CD8+ effector T cells are responsible for the clinical benefit of
CIT. This novel therapy-responsive population underlies the key cellular and molecular immunoregulatory mechanisms of chemotherapy. It serves as a meaningful marker to measure these collaborative effects and to develop the optimal chemo-immunotherapy
combination strategy.
3:00 Breakout Discussion Groups and Refreshment Break
4:00 KEYNOTE PRESENTATION: Biomarkers in Immuno-Oncology and Transitioning Them to an IVD - Opportunities and Challenges
Neeraj Adya, PhD, Director, Pharmacodiagnostics, Bristol-Myers Squibb
Precision medicine continues to transform treatment paradigms through development of new biomarkers and interpretation of clinical data. Immuno-oncology biomarkers, such as PD-L1, and emerging ones, such as TMB and GEP, may help optimize treatment
decisions, individually or in combination. The advancement of increasingly complex biomarkers also brings a need for advanced diagnostic tools. We will discuss biomarkers and their transition to an IVD in the evolving field of pharmacodiagnostics.
4:30 Is There a Role for Biomarkers in This Era of Combination Immunotherapy?
Kathleen M. Mahoney, MD, PhD, Clinical Instructor, Beth Israel Deaconess Medical Center; Research Fellow, Dana-Farber Cancer Institute
Combinations with PD-1 immune checkpoints such as chemotherapy, ipilimumab or VEGF receptor tyrosine kinase inhibitor, can improve response rates and overall survival in some tumors. In the upcoming years, the mechanisms of PD-1 resistant cancer
found in patients will be molded by the selective pressures of these therapies. Many clinical trials have investigated the toxicity and efficacy of combining PD-1 pathway blockade with other therapies. Yet few randomized Phase II studies involving
immune checkpoints have been designed to develop predictive biomarkers for these therapies. Biomarker-driven early phase trials are needed for designing Phase III trials to prospectively validate (protein or gene signature-based) biomarkers
for monotherapy or combination immunotherapy, if the pendulum is to swing back toward the development of personalized therapies with fewer toxicities.
5:00 Close of Day
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TUESDAY, AUGUST 6
7:30 am Registration Open and Morning Coffee
8:25 Chairperson’s Remarks
Michael Wichroski, PhD, Senior Principal Scientist, Immuno-Oncology, Bristol-Myers Squibb
8:30 Preclinical Characterization of BMS-986299, a First-in-Class NLRP3 Agonist with Potent Antitumor Activity, Alone and in Combination with Checkpoint Blockade
Michael Wichroski, PhD, Senior Principal Scientist, Immuno-Oncology, Bristol-Myers Squibb
Immune checkpoint inhibitors (CPI) targeting adaptive immunity have significantly improved patient outcomes in many tumor types, but other approaches are needed to extend clinical benefit to more patients. Targeting innate immunity to provide
broader activation of the immune system may be one approach to complement CPI activity. Here, we present the pre-clinical evaluation of BMS-986299, a first-in-class, NLRP3 inflammasome agonist, which shows promising combination potential with
CPI.
9:00 KEYNOTE PRESENTATION: Induction of Durable Regression in PD-1 Refractory Melanoma Following Intratumoral Injection
of a CpG-A TLR9 Agonist, CMP-001 in Combination with Systemic Pembrolizumab
Arthur Krieg, MD, Founder & CSO, Checkmate Pharmaceuticals
Checkpoint inhibitor therapies such as anti-PD-1 antibodies can induce dramatic regression of “hot” tumors, where the immune system already has been activated against the tumor but are generally ineffective against “cold”
tumors. We hypothesized that modification of the tumor microenvironment by intratumoral injection of a Toll-like receptor 9 (TLR9) agonist CpG-A oligodeoxynucleotide would convert “cold” tumors into “hot” tumors, resulting
in an increased response rate to anti-PD-1 therapy. In human clinical trials we have achieved durable tumor regression in patients with PD-1-refractory advanced melanoma.
9:30 Coordinate Targeting of Innate and Adaptive Immunity for Cancer Immunotherapies
Jon Wigginton, MD, Senior Vice President, Clinical Development & CMO, MacroGenics
10:00 Grand Opening and Coffee Break in the Exhibit Hall with Poster Viewing
10:55 Chairperson’s Remarks
Michael Wichroski, PhD, Senior Principal Scientist, Immuno-Oncology, Bristol-Myers Squibb
11:00 Assessing the Impact of Intratumoral Immune Modulation in Metastatic Melanoma
Cara Haymaker, PhD, Assistant Professor, Director, Oncology Research and Immuno-Monitoring Core (ORION), Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center
The use of innate immune modulators to improve response to checkpoint blockade holds tremendous promise for patients with solid tumors. Intratumoral administration of these agents provides a direct activation of the target innate cell(s) that
could improve antigen-presentation and subsequent anti-tumor T-cell activation. This study will demonstrate how the use of longitudinal tissue and blood collections is key to understanding both response and resistance mechanisms.
11:30 Bempegaldesleukin (NKTR-214): Accessing the IL-2 Pathway for Immuno-Oncology
Wei Lin, PhD, Senior Vice President, Oncology Development, Nektar Therapeutics
Bempegaldesleukin is an IL-2 receptor pathway agonist that stimulates rapid proliferation and activation of effector T cells, increased T cell infiltration of the tumor and sustained signaling that is maintained with successive treatment cycles,
without significantly over-activating the immune system. Bempegaldesleukin is being evaluated in combination with the checkpoint inhibitor, nivolumab, in a broad clinical program. Preliminary clinical data in melanoma and urothelial carcinoma
has demonstrated a deepening of responses over time with a favorable safety profile.
12:00 pm Close of Combination Immunotherapy
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