UCRF Strategy Refresh

Transcription

1 UCRF Strategy Refresh Clinical Caner Gene5cs (RAM lab / UNCseq / gpath) 4/16/2014

2 Cancer is a gene5c disease * Germline familial cancer syndromes pharmacogenomics Soma5c single nucleo5de variants ( muta5on ) short inser5on / dele5ons intragenic dele5ons large dele5ons / amplifica5ons structural variants (transloca5ons) DNA RNA Protein * A disease of DNA

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5 Timeline 2008 present RAM lab planning and preliminary studies UNCSeq 2012 gpath 2012 UNCSeq

6 Rapid Adop5on Molecular Lab (RAM Lab) Provides resources directly in CLIA molecular pathology lab sewng Staff Equipment Reagents Assay development / delivery in CLIA cer5fied space Mature assays Mature clinical use

7 RAM LAB Projects 1. Wash U (Ellis): PDXs and WGS Luminal tumors with AI s (n=100) 2. DFCI (Krop): Neoadjuvant Inflammatory Breast Cancers (n=80) 3. Edinborough, Scotland (Dixon): recurrence series (n=10 patent series) 4. UNC (Carey): trametnib window study with before and awer (n=15 patents) 5. Madrid, Spain (MarTn) : TNBC Neoadjuvant docetaxel/carboplatn (n=85) 6. CooperaTve Groups 1. CALGB/ALLIANCE x2 (40601 (300 HER2+) and 40603(450 TNBC)) = (~900 total samples, also two ASCO oral presentatons by Lisa Carey 2013 and 2014) 2. GEICAM (Spain): Neoadjuvant # (n=90, ASCO Oral by Aleix Prat in 2012) 3. pilot with FDA and GBG (von Minckwitz) (n=20, if good, then >1500 more) 4. pilot for TAILORx/ECOG (n=20, if good, then >2500 more) 5. pilot for TNT (metastatc TNBC 1 st line) (UK, Tuh) (n=350) 6. ECOG1199 adjuvant taxane scheduling trial (Leland- Jones) = (>2000) Nanostring work to be done (600 cases, 100 done and working on this now) 2. CBCS3 (~2000 cases to be done) 3. clinical PAM50/Prosigna offering 4. development with others (Rathmell (Renal), Kim (Bladder), Gulley (Gastric)) 5. general ncounter maintenance and miscellaneous experiments (many external PAM50 RUO requests) 6. PAM50Prosigna offering in CLIA selng for ECOG TNBC study in planning phase to enrich for Basals

8 Limita5ons Earlier stage projects Sample sets not available Technology less mature More preliminary data needed No project management or informa5cs

9 Technology Clinical Care Rapid changes in understanding of clinical cancer genetics Clinical research of Cancer Patients Ethics and regulatory considerations Tissue collecton Tissue quality Tissue type Project management Assay development

10 LCCC 1108: Development of a Tumor Molecular Analyses Program and Its Use to Support Treatment Decisions 1. To provide a mechanism for: 1. associaton of molecular alteratons (broadly defined) 2. with clinical outcome (broadly defined) in oncology 3. via genetc profiling of patent specimens (technology independent / sequencing) 2. To report results back to patent 1. Ethically compliant 2. Regulatory compliant (FDA and other) 3. Project management 1. ConsenTng and Tssue collecton 2. Tracking 3. Core transfer 4. InformaTcs

11 LCCC 1108 Execu5ve Commi^ee (Earp, Hayes, Sharpless, Grilley- Olson) Tech. Development: Hayes Chair Perou, Chiang, Sharpless, Mieczkowski, Auman, W. Kim Clinical (CCGR): Billy Kim Chair O Neil, Richards, Carey, Lee, Shores, HJ Kim, W Kim, Wu, Bae- Jump, Wang, Evans, Berg, Thomas, Ollila Earp and Grilley- Olson (ex officio) Pathology: Eberhard/Weck Chair Sharpless (ex officio) Planorm Development: Gene list for capture, reagent and plakorm needs, LIMS, muta5on calling. Clinical Use: Pa5ent lists of genes that dictate which results are reported for a clinical scenario, ethical issues related to germline analysis Technology ImplementaTon: Orthogonal tes5ng, sample collec5on and QC, billing, results repor5ng, SOPs, eventual CLIA approval

12 Produc5on Protocol office, Study staff, Tissue procurement, Clinical staff, Biospecimens processing, Pre- clinical genomics core, Genomics core, Sequencing Core, Bioinforma5cs core, Pathology

13 Production Summary Report Tue Apr 15 23:39: requested by dnhayes UNCseq Status Summary 300 active 113 sample failure Tumor 1064 consented Sample Distribution 436 completed 248 mutations reported 188 no reportable mutations Normal 215/300 distributed 227/300 distributed 35/300 pending distribution 4/300 pending distribution 49/300 not yet collected 26/300 not yet collected 0/300 not initiated 43/300 not initiated

14 Ideal Schema5c Produc5on Timeline Time to Completion Stats Early Study Total patients = 400 Physician Perception Consent to Phone Message time (344) Range:.4-16months Average: 6months Consent to Discussion (344) Range: months Average: 4.6months Sample Collection to Phone Message time (344) Range: months Average: 4.6months Processing Time Sample Collection to Discussion (344) Range: months Average: 3.3months Active Study Total patients = 539 Physician Perception Consent to Phone Message time (180) Range: months Average: 3.6months Consent to Discussion (180) Range: months Average: 2.9months Sample Collection to Phone Message time (180) Range: months Average: 2.8months Processing Time Sample Collection to Discussion (180) Range:.5-4months Average: 2.1months

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16 Future RNA gene signature and structural rearrangements DNA from blood resistance tes5ng, personalized tumor markers Clinical trials: Targeted trials referrals

17 Required Slides for Faculty Presenta5ons (I) Papers A compact VEGF signature associated with distant metastases and poor outcomes. BMC Med :9. PMCID: (PATENT LICENSED) Grants Duke-UNC-Washington University Partnership for Early Phase Clinical Trials in Cancer, (Duke PI, Herb Hurwitz, UNC PI, Claire Dees) Top three examples Total attributable to UCRF Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol Mar 10;27(8): PMCID: (PATENT LICENSED) Prediction of lung cancer histological types by RT-qPCR gene expression in FFPE specimens. J Mol Diagn Jul;15(4): PMCID: (PATENT LICENSED) > 70 % 100% UNC NCTN Integrated Translational Science (UNITS) Center. (UNC PI, Neil Hayes, Chuck Perou) Modular phase II study to link targeted therapy to patients with pathway activated tumors: Novartis Signature Trial. (UNC PI, Juneko Grilley)

18 Required Slides for Faculty Presenta5ons (II) Impact of UCRF Investment to Date Nirali Patel, MD, molecular pathology Recruitments David Eberhard, MD, molecular pathology Key UNC collaborators UNC Molecular Pathology UNC Molecular Tumor Board UNC Clinical Genetics Key external collaborators NCTN Network (ALLIANCE, NRG) Duke Washington University

19 Acknowledgements UCRF Shelley Earp Ned Sharpless