Worldwide Collaborations in Molecular Profiling

Transcription

1 Worldwide Collaborations in Molecular Profiling Lillian L. Siu, MD Director, Phase I Program and Cancer Genomics Program Princess Margaret Cancer Centre

2 Lillian Siu, MD Contracted Research: Novartis, Pfizer, BMS, Boehringer Ingelheim, Regeneron, AstraZeneca, GSK, Roche, Karyopharm Ownership Interest (stocks, stock options, or other ownership interest excluding diversified mutual funds): Agios, Entremed

3 Publically Available Genomics Related Databases 1 TCGA data portal [ data.nci.nih.gov/tcga/] Report, per disease, the data types (DNA, RNA, mirna, methylation, etc.) and omics platforms used to generate these data cbioportal [ Advanced web interface for TCGA and other largescale datasets. This tools provides access to virtually all the genomic variants called within these data

4 Publically Available Genomics Related Databases 2 My Cancer Genome at Vanderbilt [ Web interface allowing users to gain more information about specific mutations and their link to diseases and therapies; knowledge resource for personalized medicine DGIdb by WUSL [ Web interface for searching lists of genes against a compendium of drug gene interactions and potentially druggable genes

5 Selected Large Scale Clinical Molecular Profiling Programs World Wide (Bedard et al. Nature Insight 2013) 1 Institution, Consortium or Region Trial or Program Name Profiling Platform/s or Technique/s Genes and or Mutations Cancer(s) Archival or Fresh Tumour Ref And/ or Trial Iden tifier Cancer Research UK Stratified Medicine Programme PCR 9 genes Melanoma, NSCLC, CRC, Breast, Prostate, FISH 3 genes Ovarian cancer Archival 121 Dana Farber Cancer Institute PROFILE Sequenom OncoMap 41 genes, 471 mutations All solid tumours Archival 122 Institut Curie, Institut National du Cancer SHIVA Ion Torrent PGM Cytoscan HD Ampliseq 46 genes 29 genes All solid tumours Fresh biopsy NCT Institut Gustav Roussy (nonpediatric trials) Massachusetts General Hospital MD Anderson Cancer Center MOSCATO SAFIR01 MSN acgh PCR acgh PCR PCR FISH Not Applicable 96 mutations Not Applicable 2 genes Seqcan 30 genes 5 genes NS SNaP Shot 14 genes, >50 mutations Solid tumour phase I patients Breast cancer Melanoma, SCLC, NSCLC NSCLC, CRC, Melanoma, Breast cancer Fresh Biopsy Fresh Biopsy Fresh Biopsy 125 Archival 126,127 T9 Program Sequenom 40+ genes All solid tumours Archival 128 IMPACT Clearing House Protocol PCR FISH 10 genes 1 gene All solid tumours PCR ~100 genes All solid tumours Archival Archival and or Fresh Biopsy NCT NCT NCT

6 Selected Large Scale Clinical Molecular Profiling Programs World Wide (Bedard et al. Nature Insight 2013) 2 Institution, Consortium or Region Trial or Program Name Profiling Platform/s or Technique/s Genes and or Mutations Cancer(s) Archival or Fresh Tumour Ref And/or Trial Identifier Memorial Sloan- Kettering Cancer Center IMPACT Illumina HiSeq Sequenom or MiSeq 275 genes (Research assays) NS (Clinical assays) All solid tumours Archival NCT Netherlands Centre for Personalized Cancer Treatment Ion Torrent PGM SOLiD 5500xl ~150 genes >2000 genes Solid tumours Fresh Biopsy 130 Norwegian Cancer Genomics Consortium Nationwide program NS Whole Exome 9 tumour types both solid and haematopoietic Archival and or Fresh Biopsy 131 Princess Margaret Cancer Centre IMPACT MiSeq Sequenom TSACP 48 genes, >700 mutations Customized panel 23 genes, 279 mutations Selected solid tumours Archival NCT Vall D Hebron Institute of Oncology NS Sequenom Illumina GAIIx OncoCarta 19 genes, 238 mutations NS Breast cancer, Solid tumour phase I patients Archival 72,132 Vanderbilt-Ingram Cancer Center PCMI SNaPshot 6-8 genes, >40 mutations Melanoma, NSCLC, CRC, Breast cancer Archival 133 WIN Consortium WINTHER study NGS NS Solid tumours Fresh Biopsy (Tumour and Matched Normal) NCT NS = not stipulated

7 Worldwide Collaborations Harmonization and standardization Global Alliance for Genomics and Health (GA4GH) Molecular profiling trials national or international (examples) WINTHER NCI MATCH Rapid learning systems and cognitive computing platforms ASCO s CancerLinQ

8 Worldwide Collaborations Harmonization and standardization Global Alliance for Genomics and Health (GA4GH)

9 The Global Alliance for Genomics and Health Announced: June 5, 2013 with 70+ leading health care, research, and disease advocacy organizations operating in over 40 countries Current: The international alliance now stands at over 125 partner organizations Plans: to launch by early 2014, and to work towards enabling: open standards for interoperability of technology platforms for managing and sharing genomic data; guidelines and harmonized procedures for privacy and ethics internationally; stakeholders engagement to encourage responsible sharing of data and of methods.

10 GA4GH Five Working Groups Regulatory and Ethics Focus on ethics and the legal and social implications Data Data representation, storage, and analysis Security Lead the thinking on the technology aspects of data security, user access control, and audit functions Clinical Establish linkages to phenotypic and clinical (health) informatics data, and align genomic data activities with the ongoing international standards initiatives in clinical and health data Public Engagement (to be launched in early 2014) Engage patient and disease advocacy organisations; privacy advocates; and citizens

11 Clinical Working Group Topics 1. Clinical Implementation: a) Next Generation Sequencing: Overcoming barriers to implementation in the clinic b) Actionable Gene Panels for Cancer: Achieving a consensus 2. Global Matchmaking for rare tumors/ mutations 3. Phenotyping and Clinical Data: Agreeing on the right solutions and linking with genomic data

12 Worldwide Collaborations Molecular profiling trials national or international (examples) WINTHER NCI MATCH

13 Soria et al. WIN Consortium

14 NCI MATCH Trial Conley et al.

15 Worldwide Collaborations Rapid learning systems and cognitive computing platforms ASCO s CancerLinQ

16 CancerLinQ: The Future of Quality Cancer Care 16

17 Where is cancer care delivered (U.S.)? Accessed 13 October

18 The HIT Revolution in Cancer Care 2012: EHR/EMR Use in U.S. Oncology Practices Widespread adoption of EHRs by physicians and hospitals Improved data processing and storage capacities Rapid analysis tools Advances in natural language processing 14.9% 16.2% 8% 60.8% of practices already have advanced EHRs/EMRs Has basic EHR/EMR Looking to implement EHR/EMR in next 6 months No EHR/EMR Source: Forte, GJ, et al. American Society of Clinical Oncology National Census of Oncology Practices: Preliminary Report. JOP January 2013 vol. 9 no

19 Origins 19

20 What Is CancerLinQ? 20

21 Origins The primary purpose of CancerLinQ is to improve the QUALITY of care and to enhance outcomes Many other secondary benefits will be realized For Patients: Highest quality care with best outcomes for EVERY patient Clinical Trial Matching Safety Monitoring Evidence based education materials Real time side effect management Patient Portals to interact with providers and provide patient reported outcomes (PROs) 21

22 Origins The primary purpose of CancerLinQ is to improve the QUALITY of care and to enhance outcomes Many other secondary benefits will be realized For Providers: Ability to scan the system for real time second opinions Observational Clinical Decision Support (CDS) Guideline driven CDS Effectiveness Monitoring Ability to access research, literature, guidelines, etc. in real time at the point of care Quality reporting and benchmarking to avoid prior authorizations Many others 22

23 The Prototype Processing: Raw Data from Varian from Epic from Altos from Impac Transformed Data 1. Understand 2. Standardize 3. Normalize 4. Make it Available 23

24 The Prototype: Goals Reached >170,000 patients Demonstrate value added tools, such as the ability to measure a clinician s performance on a subset of QOPI measures in real time Create new ways of exploring clinical data and hypotheses generation Provide lessons learned about the technological and logistical challenges involved in a full scale CancerLinQ implementation Demonstrate ASCO s capability to develop rapid, real time, clinical decision support based on clinical guidelines and integrate them into a demonstration EHR system Demonstrate the ability to capture and aggregate complete longitudinal patient records from any source, in any format, and make use of the data 24

25 Timeline to Begin Development Process and Timeline to get to Implementation September 2013 February 2014 July 2014 RFP Prep Proposals Implement Requirements Analysis Author & Release RFP Reviews Presentations Down Selections Negotiations Prep to Start 12wks 4wks 6wks 8wks 2wks 2wks 4wks 4wks 22 weeks 16 weeks 25

26 Conclusions Large scale genomic sequencing and omics based profiling at point of care have become increasingly feasible due to advances in knowledge, technology and bioinformatics A substantial body of clinical and genomic data is being generated needs for international collaborations: Standardization Sharing and dissemination Therapeutic applications Cognitive computing and learning