Welcome to the SITC 2015 Meeting Archive
Thank you to everyone who participated in SITC's 30th Anniversary Annual Meeting & Associated Programs! The conference was once again a great success and one for the record books. More than 2,400 people from across the globe attended, making it the largest meeting in Society history.
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Access SITC 2015 Slides & Video
Global Regulatory Summit
International Symposium on Cancer Immunotherapy: Featuring Today's Innovators, Tomorrow's Leaders
SITC Primer on Tumor Immunology and Cancer Immunotherapy™
SITC Workshop on New Perspectives for Target Antigens in the Changing Cancer Immunotherapy Landscape
Immunotherapy Patient Forum for the Treatment of Melanoma, Leukemia, Lymphoma, Lung and Genitourinary Cancers
SITC 30th Anniversary Annual Meeting
Biomarkers in Cancer Immunotherapy: Oasis or Mirage?
Congratulations, SITC 2015 Award Recipients
View a complete list of award recipients here.
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Abstract Supplement Now Available in JITC
All accepted SITC 2015 abstracts have been published in a Journal for ImmunoTherapy of Cancer supplement. Access them here.
Download the 30th Anniversary Annual Meeting poster guidelines here. Contact [email protected] with any questions pertaining to the poster guidelines.
Submission Period & Details
Late-breaking abstracts are no longer being accepted. The submission period was from Monday, August 10 through Tuesday, August 25, 2015 at 5 p.m. EDT.
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- All accepted abstracts will be available to 30th Anniversary Annual Meeting attendees in printed program materials and published online in the Journal for ImmunoTherapy of Cancer
- Several oral presentation slots have been reserved for abstracts that are scientifically important and exciting to attendees; include significant advances to existing science; and are high-novelty and provide teaching moments
- All accepted abstracts not selected for oral presentation will be included as poster presentations
Abstract submission is now closed. The deadline for submissions was July 14, 2015 (5 p.m. EDT).
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Immune biomarkers associated with clinical benefit from atezolizumab (MPDL3280a; anti-PD-L1) in advanced urothelial bladder cancer (UBC)
30th Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2015)
- Poster presentation
- Open Access
- Thomas Powles1,
- Dorothee Nickles2,
- Eliezer Van Allen3,
- Colombe Chappey2,
- Wei Zou2,
- Marcin Kowanetz2,
- Edward Kadel2,
- Mitchell Denker2,
- Zachary Boyd2,
- Nicholas Vogelzang4,
- Joseph Kim5,
- Joaquim Bellmunt3,
- Yohann Loriot6,
- Charles G Drake7,
- Carol O'Hear2,
- Marcella Fasso2,
- Priti Hegde2 &
- Sanjeev Mariathasan2
Journal for ImmunoTherapy of Cancervolume 3, Article number: P83 (2015) Cite this article
Atezolizumab (anti-PD-L1) has demonstrated robust clinical activity in UBC . Elevated PD-L1 expression on tumor-infiltrating immune cells (IC) is associated with increased clinical efficacy; however, the contribution of other immune biomarkers is unknown. In this study, we explored tumor-based and circulating biomarkers and their correlation with clinical benefit in atezolizumab-treated patients with UBC.
Patients from the UBC cohort (n = 92) of the Phase Ia atezolizumab trial PCD4989g (NCT01375842) served as source population for tumor specimens, plasma and PBMC. Baseline tumor PD-L1 expression was assessed by immunohistochemistry using the SP142 antibody assay optimized to detect PD-L1 on both tumor cells (TC) and IC. RNA gene expression on tumor and PBMC samples was interrogated with a NanoString panel of 800 immune and cancer genes. Sequential blood draws assessed dynamic changes in circulating immune biomarkers in plasma (RBM, Multi-Analyte Platform). Correlation between biomarker expression and 6-month progression-free survival (PFS; as a measure of clinical benefit) was assessed.
Baseline gene expression in tumors revealed an effector T cell signature (including CD8A, GZMA, IFNG) and NK gene signature (NKG2 family members) associated with clinical benefit. In contrast, disease progression was associated with either a concomitant presence of the immune signature and an opposing stromal signature (PDPN, COL5A1, etc) or the absence of both signatures. Expression of T cell effector and immune checkpoint genes (CTLA4, PD-1, TIGIT, LAG3) correlated with PD-L1 expression on IC but not TC. Increased expression of myeloid-derived cytokines (IL-6 and IL-8) in the plasma was associated with lack of clinical benefit. Moreover, on-treatment sampling revealed an increased plasma HCG, CA15-3 and TIMP-1 to be correlated with disease progression. Immune biomarkers associated with PBMC, as well as tumor biomarkers associated with various tumor subtypes, will also be discussed.
Our findings indicate that clinical benefit (as defined by 6-month PFS) from atezolizumab is influenced by a pre-existing CD8+ effector T cell and NK cytolytic gene signature in the tumor, which correlated with IC PD-L1 expression. Increased stromal and myeloid-derived cytokine expression in tumor and plasma, respectively, were associated with lack of clinical benefit, underscoring the complex interplay among immunological components in UBC. These components may be conceivable targets to overcome potential resistance and promote response to atezolizumab.
ClinicalTrials.gov Identifier: NCT01375842
Powles T, Eder JP, Fine GD, Braiteh FS, Loriot Y, Cruz C, et al: MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014, 515 (7528): 558-562.
PubMedCASArticle Google Scholar
Barts Cancer Institute, Queen Mary University of London, London, UK
Genentech, Inc., South San Francisco, CA, USA
Dorothee Nickles, Colombe Chappey, Wei Zou, Marcin Kowanetz, Edward Kadel, Mitchell Denker, Zachary Boyd, Carol O'Hear, Marcella Fasso, Priti Hegde & Sanjeev Mariathasan
Dana-Farber Cancer Institute, Boston, MA, USA
Eliezer Van Allen & Joaquim Bellmunt
US Oncology Research, Comprehensive Cancer Centers, Las Vegas, NV, USA
Yale Cancer Center, New Haven, CT, USA
Gustav Roussy Institute of Oncology, Paris-Sud University, Paris, France
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA
Charles G Drake
Correspondence to Thomas Powles.
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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Powles, T., Nickles, D., Van Allen, E. et al. Immune biomarkers associated with clinical benefit from atezolizumab (MPDL3280a; anti-PD-L1) in advanced urothelial bladder cancer (UBC). j. immunotherapy cancer3, P83 (2015). https://doi.org/10.1186/2051-1426-3-S2-P83
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- Immune Checkpoint
- Urothelial Bladder Cancer
- SP142 Antibody
- Stromal Signature
- Baseline Gene Expression
Highlights from SITC's 31st Annual Meeting & Associated Programs
The development of novel immune-based cancer treatment options is the result of a dramatic increase in our understanding of tumor immunology. This 1-day educational program provided a foundation in core immunology principles for students and postdoctoral fellows, and provided more senior physicians and scientists with the opportunity to solidify their understanding of immuno-oncology as it relates to basic and clinical research in cancer immunotherapy.
Workshop on Challenges, Insights, and Future Directions for Mouse and Humanized Models in Cancer Immunology and Immunotherapy Disease models are important tools to inform the future of immune drug development and aid our understanding of the mechanisms underlying antitumor immune responses. This workshop provided a comprehensive discussion on the strengths and weaknesses of a variety of models, approaches toward improving the predictive value of mouse models, and anticipated advances in cancer modeling, with a focus on how to accurately model the tumor immune microenvironment.
SITC 2016 31ST ANNUAL MEETING
Presented by leaders in the field, this year’s plenary sessions addressed topics central to progress in tumor immunology and cancer immunotherapy, including the tumor microenvironment, state-of-the-art immunotherapies, the future of combination immunotherapy, and high-priority agents under investigation in the Cancer Immunotherapy Trials Network (CITN). In addition, the 31st Annual Meeting featured a number of thought-provoking concurrent sessions, 2 of which were interdisciplinary programs organized in collaboration with the American Society for Cell Biology and the Society of Behavioral Medicine.
Value of Cancer Immunotherapy Summit
Building on the success of the SITC 2015 Value of Cancer Immunotherapy Session, this half-day program, which was organized in collaboration with the American Society of Clinical Oncology, united experts in cancer immunotherapy with key stakeholders in the healthcare system, and also provided a patient perspective. Presenters emphasized that the unique aspects of immune-based agents will affect the real value of these therapies and helped prioritize the direction of future discussions on the value of cancer immunotherapy. Based on the outcomes of this summit, SITC will continue its efforts to optimize the value framework for cancer therapeutics to ensure patients have access to high-quality, cost-effective care.
Abstracts featuring cutting-edge data from basic and translational research, clinical trials, and aspects of clinical management were presented throughout the meeting. Some of the most novel and practice-changing clinical trials are highlighted below.
In a highly anticipated presentation, Joaquim Bellmunt, MD, PhD, of Dana-Farber/Brigham and Women’s Cancer Center, shared data on the effects of pembrolizumab (Keytruda) versus investigators’ choice of standard chemotherapy agents for the treatment of advanced bladder cancer. This international study reported significantly longer overall survival in patients treated with pembrolizumab (HR, 0.73; P = .0022; median 10.3 vs 7.4 months), and this was seen across all PD-L1 populations. This study was halted prematurely due to the markedly superior response in patients treated with pembrolizumab and is noteworthy in being the first in almost 20 years to demonstrate improved overall survival for patients with advanced bladder cancer.
Interim data from a multicenter phase I/II trial investigating 2 dose schedules of ipilimumab (Yervoy) and nivolumab (Opdivo; 1 mg/3 mg vs 3 mg/1 mg) in patients with advanced or metastatic urothelial cancer that progressed after chemotherapy were presented by Padmanee Sharma, MD, PhD, of The University of Texas MD Anderson Cancer Center. Patients in the nivolumab 1/ ipilimumab 3 arm had an objective response rate (ORR) of 38.5%, while ORR in the nivolumab 3/ipilimumab 1 and nivolumab monotherapy arms were 26.0% and 25.5%, respectively. Median overall survival was also higher in the nivolumab 1/ipilimumab 3 group (10.2 months [95% CI, 4.5-not reached]) than the nivolumab 3/ipilimumab 1 group (7.3 months [95% CI, 5.6-11.4]). Side effects in the combination treatment groups were similar to those observed in other studies. These results support further development of the nivolumab 1/ipilimumab 3 combination for treatment of metastatic urothelial cancer.
John Hunter, PhD, of Compugen Inc, presented findings from an international study that used proprietary computational algorithms to identify a potential new T-cell checkpoint, PVRIG. PVRIG is a member of the TIGIT molecular family that is expressed on T cells and NK cells. The Compugen group also developed an anti- body specific for PVRIG, which enhanced CD4+ and CD8+ T cell proliferation in vitro and significantly reduced tumor growth when combined with antiPD-1 therapy growth (P = .0005; 56% tumor growth inhibition) in vivo. New immunotherapeutic targets, such as PVRIG, that can be used in combination might help expand the proportion of patients who respond to treatment with immune checkpoint inhibitors.
SITC Initiatives: Updates From the Immune Biomarkers Task Force and Immunoscore Validation Project
SITC President and Immune Biomarkers Task Force Chair Lisa Butterfield, PhD, of the University of Pittsburgh, reported recent progress from the SITC Immune Biomarkers Task Force, which was established to address novel topics in the field, including technologies and high-throughput approaches, novel and conventional agents affecting immunity, bioinformatics, complex data analysis, and advances in biological sampling. From 2015 to 2016, 4 working groups (WGs) sought to address challenges barring progress in the field. In this ongoing effort, these WGs have generated 5 white papers and led a dedicated workshop, Immunotherapy Biomarkers 2016: Overcoming the Barriers, held in collaboration with the National Institutes of Health. In addition, the WGs also authored 12 short reports highlighting novel technologies used for biomarker development in a series published in the Journal for Immunotherapy of Cancer.
As an update to the results presented at ASCO 2016, Jérôme Galon, PhD, of INSERM, presented the latest results of the SITC Immunoscore Validation Project, a SITC-led international effort to validate the Immunoscore, which is a standardized immunohisto-chemistry-based assay to measure the immune contexture in and around tumors. As presented previously, the primary objective of this study in patients with stage I-III colon cancer was reached; Immunoscore high versus low predicted time to recurrence in each of the separate groups examined. New data were also presented, in which Immunoscore was predictive of overall and disease-free survival independent of MSI status (high vs low). These findings illustrate the prognostic value of Immunoscore and justify the use of immune parameters as a new component of cancer classification.
.MILAD SITC 2015
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