Cambridge Healthtech Institute 第2屆

Combination Immunotherapy

( 合併免疫療法 )


2018年6月11 - 12日 | Westin Boston Waterfront | 馬薩諸塞州波士頓

癌症免疫療法藥物開發未來焦點將放在合併療法,透過和其他可期相乘效果的免疫療法、標靶治療的合理合併使用,其正於各種免疫療法模態進行測試。若是合併免疫療法,可能達成既有方法難以實現的長期延長壽命成效。本會議以癌症免疫療法、傳統癌症治療及其他免疫療法、標靶療法及其最有效之合併療法等為主題,藥廠及學術機構等主要研究人員將分享作用機制、毒性管理、可期待相乘效果的合併療法設計策略、生物標記開發等議題,並介紹目前進行的合併免疫療法研究案例。

Final Agenda

Sunday, June 10

4:30-6:30 pm Short Course and Conference Registration

5:00-8:30 Dinner Short Course*

SC1: Fit-for-Purpose Biomarker Assay Development and Validation

*Separate registration required

Monday, June 11

7:00 am Conference Registration and Morning Coffee

8:00 Organizer's Welcome

 

OPENING PLENARY SESSION: EMERGING APPROACHES FOR CANCER

8:05 Chairperson's Opening Remarks

George A. Green, IV, PhD, Head, Pharmacodiagnostics, Bristol-Myers Squibb

8:10 Clinical Genomic Profiling Using the MSK-IMPACT™ Large Panel NGS Assay to Guide Patient Selection for Targeted and Immune Therapies

Marc Ladanyi, MD, William J. Ruane Chair in Molecular Oncology, Molecular Diagnostics Service and Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center

As the centerpiece of an institutional initiative in clinical cancer genomics, we have implemented large scale genomic profiling for targetable cancer drivers and other cancer-relevant alterations in all patients with advanced solid cancers. Since 2014, over 23,000 patients have been profiled using the MSK-IMPACT™ targeted large panel, capture-based DNAseq assay. MSK-IMPACT™, which received FDA clearance in 2017, allows robust detection of somatic mutations in all known cancer genes, copy number changes and select cancer fusion gene rearrangements, as well as assessing overall tumor mutation burden and microsatellite instability. Patients are also screened for oncogenic fusions by targeted RNAseq and for germline cancer predisposition alleles and evidence of clonal hematopoiesis.

8:40 Widgets to Cancer Patient-Specific Digits: The Case for Out-of-Clinic Objective Measures and Their Potential Impact to Remote Patient Monitoring in Precision Oncology and Discovery

Christopher M. Hartshorn, PhD, Program Director, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health

Albeit the case for long-term, out-of-clinic monitoring has been obvious for many chronic diseases, the case for cancer has not been as clear. The National Cancer Institute has begun piloting and funding various aspects to enable an Internet of Cancer Medical Things. This talk will focus on these efforts currently and prospectively as well as the overall vision to coordinate a much broader initiative to improve our understanding of cancer progression and improve the delivery of cancer care.

9:10 Coffee Break in the Exhibit Hall with Poster Viewing

 

BIOMARKERS FOR COMBINATION IMMUNOTHERAPY

9:55 Chairperson's Remarks

Carol Anne Ogden, PhD, Senior Manager and ADCETRIS Biomarker Lead, Diagnostics and Biomarkers, Seattle Genetics, Inc.

10:00 Looking under the Spotlight: Evaluation of Biomarkers in an ADC + CPI Combination Clinical Trial

Carol Anne Ogden, PhD, Senior Manager and ADCETRIS Biomarker Lead, Diagnostics and Biomarkers, Seattle Genetics, Inc.

Brentuximab vedotin (BV) is an antibody-drug conjugate directed against CD30, a receptor expressed by malignant Reed-Sternberg (RS) cells present in classical Hodgkin lymphoma. Treatment with BV may result in inflammatory activity due to RS destruction by immunogenic cell death. Nivolumab blocks the programmed death-1 (PD-1) receptor, inhibiting the binding of PD-1 ligands, and together with the inflammatory activation activity of BV, restores the antitumor immune response.

10:30 Considerations for PK/PD Analysis in Optimal Dose Selection of Novel Immune Checkpoint Combinations

Vladimir Jankovic, MD, Director, Precision Medicine, Early Clinical Development & Experimental Sciences, Regeneron

As the expanding portfolio of novel immune checkpoint combinations enters the clinic, investigating a broad dose combination matrix in Phase II efficacy studies will not be efficient. Novel PK/PD analysis approaches to narrow down the range of safe and effective IO combination regimens during Phase I dose escalation are needed to streamline the proof-of-concept studies.

11:00 Forward and Reverse Strategies to Support the Clinical Development of the Anti-PD-1 Antibody Pembrolizumab

Sarah Javaid, PhD, Associate Principal Scientist, Merck

Immune checkpoint blockade therapies are revolutionizing the standard cancer treatment. Despite the current success of these therapies, not all patients respond to immunotherapy and even those that do often experience toxicities. Combination approaches are the keys to improving clinical response. Novel high throughput technologies enable us to understand the mechanisms underlying the complex interactions between the immune system and cancer, identify predictive biomarkers for the patients who will most likely benefit from current immunotherapies, avoid immune-related adverse events and reduce treatment costs for those unlikely to respond.

11:30 Sponsored Presentation (Opportunity Available)

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

 

RATIONAL COMBINATION IMMUNOTHERAPY STRATEGIES

1:25 Chairperson's Remarks

Emmett Schmidt, PhD, Distinguished Scientist & Executive Director, Merck Research Labs

1:30 Drivers in the Clinical Development of Cancer Combination Therapy

Emmett Schmidt, PhD, Distinguished Scientist & Executive Director, Merck Research Labs

Immune checkpoint inhibition is emerging as a backbone for cancer therapy. Data from a broad range of combination trials containing such therapies have emerged in the last three years. Combination benefit by independent action and through molecular reasoning both fit portions of these developing results. A flexible application of both approaches to future trial development seems likely to yield rewards in combination therapy development.

2:00 Shifting Perspectives on Combination Immunotherapy

Maria Karasarides, PhD, Executive Director, Immuno-Oncology, Regeneron Pharmaceuticals

2:30 Dual Checkpoint Inhibition DART® Molecules

Sadhna Shankar, MD, MPH, Senior Director, Clinical Research & Development, MacroGenics

Combinations of multiple checkpoint inhibitors have resulted in significantly enhanced benefit compared to the blockade of a single target. DART molecules are designed to simultaneously bind to two targets. MGD013 (co-blockade of PD-1 and LAG-3) and MGD019 (co-blockade of PD-1 and CTLA-4), are DART molecules that could deliver biological and clinical activity of combined checkpoint blockade using a single molecule with potential advantages in biology, clinical development and patient convenience.

3:00 Sponsored Presentation (Opportunity Available)

3:30 Refreshment Break in the Exhibit Hall. Last chance for poster viewing.

 

PERSONALIZED VACCINES: POTENTIAL FOR COMBINATION IMMUNOTHERAPY

4:10 Chairperson's Remarks

Emmett Schmidt, PhD, Distinguished Scientist & Executive Director, Merck Research Labs

4:15 Cancer Vaccines: Advances, Challenges and Opportunities

Marijo Bilusic, MD, PhD, Associate Research Physician, National Cancer Institute, National Institutes of Health

Therapeutic cancer vaccines are unlikely to impact treatment outcomes as monotherapy. There is growing preclinical and clinical data that combination with other treatment modalities like chemotherapy, hormone therapy or immunotherapy can enhance treatment efficacy and induce immunogenic intensification with minimal additional toxicity. It seems that therapeutic vaccines with checkpoint inhibitors holds the greatest potential for improving clinical outcomes.

4:45 The Next Wave: Combination Immunotherapy with Vaccines Targeting a New Class of Cancer Antigens, Combined with T Cell Agonists and Checkpoint Blockers

Bernard A. Fox, PhD, Harder Family Chair for Cancer Research, Member and Chief, Laboratory of Molecular and Tumor Immunology, Robert W. Franz Cancer Center, Earle A. Chiles Research Institute, Providence Portland Medical Center; CEO, UbiVac

Using a microvesicle vaccine composed of SLiPs and DRiPs, and termed DRibbles (DRiPs in Belbs), in a tumor model that lacks apparent immunogenicity, and where anti PD-L1 has no effect, we find that DRibble vaccination combined with anti-OX40 can substantially boost therapeutic efficacy and result in apparent cure of animals. We have performed a Phase II trial of this strategy as adjuvant treatment for definitively treated NSCLC and document induction or boosting of immune response to a wide spectrum of proteins whose genes are overexpressed in NSCLC.

5:15 Dissecting Immune Correlates in Cancer Immunotherapy Clinical Trials

Steven Fling, PhD, Senior Staff Scientist, Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center; Director, Cancer Immunotherapy Trials Network Immune Monitoring Laboratory

Our lab coordinates multi-parameter, immune monitoring of multi-center cancer immunotherapy trials. We recently reported clinical results from a vaccine therapy trial in cancer patients with advanced malignancies expressing NY-ESO-1, showing significantly increased humoral and cellular immunity resulting from the vaccine regimen. Here we report techniques and in-depth results dissecting multiple correlates associated with the enhanced immune response to vaccine, including gene signatures and delineation of antigen presenting cell subsets.

5:45 Welcome Reception in the Exhibit Hall with Poster Viewing

Tuesday, June 12

7:25 am Interactive Breakout Discussion Groups with Continental Breakfast

 

TARGETING THE TUMOR MICROENVIRONMENT: ACTIVATING THE IMMUNE SYSTEM FOR BETTER RESPONSE TO IMMUNOTHERAPY

8:25 Chairperson's Remarks

John Milburn Jessup, MD, George Mason University

8:30 Deep Primed™ Immunotherapy: Controlling the Microenvironment in T Cell Therapy

Ulrik B. Nielsen, PhD, President and Co-Founder, Torque

Torque is developing Deep Primed™ cell therapies that direct and evoke immune responses in the tumor and immune microenvironment. The Torque platform makes it possible to anchor powerful stimulatory cytokines, antibodies, and small molecules directly to immune cells to direct their activity and increase their efficacy and durability in the "hostile" tumor microenvironment, while controlling systemic exposure. Torque's lead product candidate is Deep IL-15, which is entering clinical development for hematologic and solid tumors.

9:00 Modulating Intratumoral Myeloid Cells to Prime Responses to Anti-PD-1 Blockade

Robert Pierce, MD, Scientific Director, Immunopathology Core, Fred Hutchinson Cancer Research Center

Anti PD-1 blockade is effective in many solid tumors, but response appears to be predicated on a preexisting anti-tumor T cell response. Immunologically quiescent tumors generally fail to respond. The tumor microenvironment (TME) of these poorly inflamed tumors are often dominated by myeloid-derived (MF) immunosuppressive cells. Using experimental mouse models and human tumor samples, we describe various immunosuppressive states of intratumoral MF and potential means to reverse the immunosuppressive TME through modulating these cells.

9:30 Targeting the DNA Damage Response to Enhance Immunotherapeutics

Timothy Yap, MD, PhD, Associate Professor, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center

DNA damage response agents, such as PARP inhibitors, are widely used in clinical oncology and exploit deficiencies in tumor DNA repair. Given the expanding role of immune checkpoint inhibitors in cancer medicine, the interaction of tumor DNA damage with the immune system has recently come into focus. It is now clear that the tumor DNA repair landscape has a key role in driving antitumor response to immune checkpoint blockade.

10:00 Immunogenic Cell Death: An Agnostic Adjuvant for Mice and Men

John Milburn Jessup, MD, Scientific Director, Precision Cancer Care Program, Inova Schar Cancer Institute; Professor, Systems Biology, Krasnow Institute of Advanced Study, George Mason University

Immunogenic cell death is a form of necroptosis caused by viruses, select cytotoxic agents and radiation that causes the release of tumor antigens in association with eat me and take me signals that promote innate immunity as well as cross-prime adaptive immune responses to the tumor. The advantage of this approach is that it is agnostic to the specific tumor antigen and stimulates the host to determine what may be important as an immune response. Our approach in human and mouse colorectal carcinoma involves combining a viral therapeutic with a standard cytotoxic agent to induce cell-mediated immunity to tumor antigens that then may be augmented by checkpoint inhibitors.

10:30 Coffee Break in the Exhibit Hall with Poster Viewing

 

TUMOR NEOANTIGENS AS BIOMARKERS AND TARGETS

11:10 Chairperson's Remarks

Fred Ramsdell, PhD, Parker Institute for Cancer Immunotherapy

11:15 Neoantigens and Their Relationship to Mutational Load, Mismatch Repair and Immune Checkpoint Expression

Arnold B. Gelb, MD, MS, FASCP, FCAP, Clinical Advisor, Exploratory Biomarkers

The objectives of this presentation are: 1) to review the biological background by which somatic mutations can lead to the generation of private, highly immunogenic tumor antigens (neoantigens), 2) to discuss association of neoantigens with mutational burden, mismatch repair and immune checkpoint expression, and 3) to provide an outlook on clinical applications involving assessment of neoantigens and mutational load with regards to response to immune-checkpoint blockade in solid tumors.

11:45 Tumor Neoantigen Selection Alliance (TESLA): Towards Personalized Cancer Vaccines

Fred Ramsdell, PhD, Vice President, Research, Parker Institute for Cancer Immunotherapy

It is now accepted that mutation-derived neoantigens can elicit a tumor-specific immune response. Identifying neoantigens accurately from the exome sequence is a key parameter for the development of such responses and remains a significant variable of the overall process. TESLA is a consortium-based approach involving over 30 groups to identify key parameters in neoantigen prediction. An update on the progress of the program will be discussed.

12:15 pm Driving CD8+ T Cell Responses to Mutational Neoantigens in Tumors-Harnessing Immunogenic Viral Vectors in Combination with Immune Checkpoint Modulators

Karin Jooss, PhD, CSO, Gritstone Oncology

DNA damage may cause mutations in tumors that can generate new antigens, known as tumor-specific neo-antigens (TSNAs). Accurate prediction of TSNAs is key to generate potent TSNA specific vaccine approaches. Viral vector-based vaccine platforms have shown to induce hi-titer, polyfunctional and durable CD4+ and CD8+ T cell responses in humans. The personalized vaccine is delivered in combination with immune checkpoint blockade, to keep TSNA-induced T cells active in the immunosuppressive tumor microenvironment.

12:45 Close of Conference

* 活動內容有可能不事先告知作更動及調整。