Cambridge Healthtech Institute’s 7th Annual

Combination Cancer Immunotherapy
( 併用免疫療法 )

有効性の向上と耐性の低減に向けた合理的な併用戦略

2019年8月5日~6日



併用免疫療法をテーマにしたこのカンファレンスプログラムでは、がん免疫療法と従来のがん治療や他の免疫療法、標的療法との効果的な併用法について考えます。

Final Agenda

8月5日(月)

7:30 am Registration Open and Morning Coffee

チェックポイント調節因子に対する反応性の向上を目的とした併用戦略

8:25 Chairperson’s Opening Remarks

Rakesh Dixit, PhD, DABT, Vice President, R&D; Global Head, Biologics Safety Assessment, MedImmune


8:30 KEYNOTE PRESENTATION: Immunotherapy Combinations: Challenges and Opportunities

Rakesh Dixit, PhD, DABT, Vice President, R&D; Global Head, Biologics Safety Assessment, MedImmune

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 α-PD-1 based immunotherapy combinations, 2) learning from early phase clinical trials investigating α-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

免疫療法の各種モダリティの併用

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 Turbocharging Efficacy: Combinatorial Approaches with CD19 CAR Ts

David Fontana, Head, Strategic Alliance & JCAR017 Program Lead, Juno Therapeutics

CD19 CAR Ts have demonstrated notable activity in DLBCL, CLL, ALL and other hematological malignancies with high overall response rates and durable CRs. However, a portion of patients either do not respond or their responses are not durable. Learnings from non-responders or CAR-T relapses are providing data into the multitude of potential resistance/suppressive mechanisms. This presentation will review combination approaches being evaluated to overcoming resistance in CAR T to improve outcomes in NHL and provide insights for solid tumor approaches and the next wave of targets.

11:30 Sponsored Presentation (Opportunity Available)

12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:30 Session Break

免疫療法と他のがん治療の併用

1:25 Chairperson’s Remarks

Rakesh Dixit, PhD, DABT, Vice President, R&D; Global Head, Biologics Safety Assessment, MedImmune

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

併用免疫療法を誘導するバイオマーカー

4:00 TMB/GEP Dual Biomarker Strategy for Personalized Checkpoint Blockade Combination Immunotherapy

Jianda Yuan, MD, PhD, Senior Director, Translational Oncology, Merck

Immune checkpoint blockade therapies are revolutionizing the standard cancer treatment. Despite the current success of these therapies, not all patients respond to immunotherapy. Combination approaches are the keys to improving clinical response. Tumor mutational burden (TMB) and gene expression profile (GEP) are emerging biomarkers predicting patient response. Dual TMB/GEP biomarkers allow us to understand novel translational biomarkers to stratify patients effectively for personalized cancer immunotherapy.

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

8月6日(火)

7:30 am Registration Open and Morning Coffee

自然免疫の標的化によるチェックポイント調節因子に対する反応性の向上

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 Sponsored Presentation (Opportunity Available)

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

* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。

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