Caris Life Sciences, Inc. · NASDAQ:CAI
Caris Life Sciences — Society of Surgical Oncology Annual Meeting 2015
19 slides from Caris Life Sciences's conference presentation, Mar 27, 2015
Slide 1: Comprehensive multiplatform biomarker analysis of 313 hepatocellular carcinomas identifies potential novel therapeutic options
Comprehensive multiplatform biomarker analysis of 313 hepatocellular carcinomas identifies potential novel therapeutic options Ghassan Abou-Alfa, MD, John T. Miura, MD, Clark Gamblin, MD, MS, Ruth He, MD, PhD, Joanne Xiu, PhD, Sherri Z. Millis, MS, PhD, Zoran Gatalica, MD, DSc, Sandeep K. Reddy, MD,
Slide 2: Disclosures
Disclosures • Support for this study was provided by Caris Life Sciences • Celina Ang: Advisory board - Bayer/Onyx, Caris Life Sciences; Travel support – Caris Life Sciences • Ghassan Abou-Alfa: Consulting: Abbott Laboratories, Amgen, Bayer, Clovis, Eli Lilly and Company/Imclone, Exelixis, Genentech
Slide 3: Disclosures
Disclosures • John T Miura: none • Ruth He: none • Joanne Xiu: employee of Caris Life Sciences • Sherri Z Millis: employee of Caris Life Sciences • Zoran Gatalica: employee of Caris Life Sciences • Sandeep Reddy: employee of Caris Life Sciences • Nelson Yee: none
Slide 4: Therapy for Advanced Hepatocellular Carcinoma
Therapy for Advanced Hepatocellular Carcinoma • Sorafenib is the only active agent Negative phase III trials in HCC • Multiple negative trials Agent Trial/Setting Sorafenib STORM – vs placebo, adjuvant • No predictive biomarkers Sunitinib vs sorafenib, 1st line • Rationale for molecular profiling Er
Slide 5: Study Design and Objective
Study Design and Objective • Design: Retrospective review of HCC molecular profiling data generated by multiplatform analysis • Objective: To describe molecular patterns and associations, and potential novel therapeutic targets in HCC
Slide 6: Methods
Methods • Formalin-fixed paraffin-embedded samples • Multiplatform profiling at CLIA certified lab • Specimens reviewed by board-certified pathologists • Immunohistochemistry (IHC) – 21 protein panel – Slides stained using automated system (Ventana Medical Systems, Tucson, AZ) as per manufacturer’s
Slide 7: Methods (cont.)
Methods (cont.) • Fluorescence/chromogenic in situ hybridization (FISH/CISH) – Detect gene amplifications – Standard scoring systems applied • DNA sequencing (Next generation sequencing or Sanger sequencing) – 47 genes – NGS using Illumina MiSeq platform (Illumina TruSeq Amplicon Cancer Hotspot pane
Slide 8: Results
Results
Slide 9: Specimens
Specimens • 313 individual patient specimens • Heterogeneous • Median age 61 years (18-87 years) • Male:female ratio = 2.7:1 • Metastases in 36% of subjects
Slide 10: Changes in gene copy number by FISH or CISH
Changes in gene copy number by FISH or CISH Percent Positive 10 5 0 cMET EGFR (2/87) Her2 (9/96) TOP2A (5/164) (0/13)
Slide 11: Protein expression by IHC
Protein expression by IHC Percentage of samples with change in protein expression, by IHC High expression levels Low expression levels EGFR TOPO1 PD-1 TOP2A SPARC cMET RRM1 TS PTEN MGMT 58 52 52 36 35 25 82 80 66 32
Slide 12: Protein expression in primary and metastatic tumors
Protein expression in primary and metastatic tumors • Significantly higher numbers of PD-1+ tumor infiltrating lymphocytes in metastatic lesions (p = 0.0128) • Low TS (thymidylate synthase) significantly more frequent in primary tumor (p = 0.0004) – Low TS associated with sensitivity to fluoropyrimi
Slide 13: Incidence of gene mutations
Incidence of gene mutations Genes without mutations ALK FGFR1 MLH1 APC FGFR2 MPL BRAF FLT3 Notch1 PERCENTAGE CDH1 GNA11 NPM1 c-Kit GNAQ PDGFRA CSF1R GNAS RET EGFR HNF1A SMAD4 ERBB4 HRAS SMARCB1 FBXW7 JAK2 VHL VEGFR2 BRCA1
Slide 14: Co-incidence of gene alterations and protein expression by CTNNB1 mutation status
Co-incidence of gene alterations and changes in protein expression by CTNNB1 mutation status N = 18 N = 59
Slide 15: Co-incidence of gene alterations and protein expression by TP53 mutation status
Co-incidence of gene alterations and changes in protein expression by TP53 mutation status 50 140 45 120 40 35 100 # of Mutations % Expression TP53 MT 30 80 25 TP53 WT 60 20 15 40 10 20 5 0 0 TOPO2A TS RRM1 PIK3CA PTPN11 RB1 PTEN AKT1 IDH1 CTNNB1 cMET ABL1 ATM NRAS ERBB2 JAK3 STK11
Slide 16: Actionable Targets
Actionable Targets • EGFR - SEARCH (sorafenib + erlotinib vs sorafenib) negative • PI3K/Akt/mTOR - EVOLVE (everolimus vs placebo) negative • PD-1 – phase I nivolumab (NCT01658878) • Wnt - Phase 1b sorafenib + ipafricept (NCT02069145) – Combination therapy with anti-androgens or taxane? • C-Met – pha
Slide 17: SEARCH (sorafenib + erlotinib)
SEARCH (sorafenib + erlotinib)
Slide 18: Conclusions
Conclusions • Novel therapeutic targets and potential combinations identified • Findings supported by existing literature • Needs clinical validation
Slide 19: Acknowledgements
Acknowledgements • Co-authors • Sherri Millis, MS, PhD • Patients • Celina.ang@mssm.edu
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