5 2015.11.13 II Precision medicine SCRUM-Japan EPOC
SCRUM-Japan 20152 20173 2250 186 20 20159 IRB NGS ; Oncomine Cancer Research Panel143 CLIA 2TAT 14
Central Testing at CLIA Labs Oncomine Cancer Research Panel Genome data Commission Advisory board Dr. T. Noda (JFCR) Dr. H. Mano (UTokyo) Dr. T.Yamori (PMDA) Genome data Annotated report Clinical Specimen LC-SCRUM-Japan LC R SCRUM-Japan NCC Management Office Contract, COI Accounting EPOC-TR Data Center Clinico-genome database GI-SCREEN- Japan Annotated report Funding Contract Anonymized data Clinical Specimen Astellas AstraZeneca Amgen Eisai Ono Kyowa Kirin MSD LC-SCRUM Participating Centers Daiichi- Sankyo Taiho Takeda Chugai Pfizer Novartis Eli Lilly 186 sites 20 core sites GI-SCREEN Participating Centers
Company A Clinical Trials Company A Clinical Trials Investigatororiented Decision Company B Clinical Trials Company C Clinical Trials Company D Clinical Trials Company E Clinical Trials Company F Clinical Trials IITs + SCRUM-Japan provides detailed information of each trial. Company B Clinical Trials Company C Clinical Trials Company D Clinical Trials Company E Clinical Trials Company F Clinical Trials IITs + Investigatororiented Decision + Investigator-initiated Trial
20159 LC-SCRUM 411 GI-SCREEN 311 94.0 179 91.3 Colorectal Cancer (282) Non-CRC (267) 179 91.8 FFPE Small panel
Oncomine Cancer Research Panel Workflow CLIA
LC-SCRUM, 20159 1 (1-90 ) OCP target genes Variant of Uncertain Significance (1-170) DB SNP 7 311
Actionable mutation http://epoc.ncc.go.jp/scrum/
Clinical Trials Targeting Genomic Alterations Screened in LC-SCRUM-Japan Target Agent Phase Sponsor Status RET fusion Vandetanib P2 IIT Completed RET fusion Lenvatinib (E7080) P2 Eisai Completed ROS1 fusion Crizotinib P2 OxOnc Completed ALK fusion CH5424802 vs. Crizotinib P3 Chugai Completed ALK fusion (stage II/III) LDK378 P2 IIT Ongoing ALK fusion (crizotinib induced NV) Granisetron+dexamethasone P2 IIT Ongoing BRAF mutation Dabrafenib + Trametinib P2 GSK (Novartis) Ongoing PIK3CA mutation, AKT1 mutation AZD 5363 P1 AstraZeneca Ongoing PIK3CA mutation BYL719 P1 Novartis Ongoing PI3K/AKT mutation TAS-117 P1 Taiho Ongoing FGFR mutation TAS-120 P1 Taiho Ongoing FGFR mutation ASP5878 P1 Astellas Ongoing FGFR alterations BGJ398 P1 Novartis Ongoing cmet amplification INC280 P2 Novartis Ongoing HER2 alterations Trastuzumab P2 IIT Ongoing HER2 alterations Trastuzumab Emtansine P2 IIT Ongoing KRAS mutation Abemaciclib vs. erlotinib P3 Eli Lilly Ongoing Dr. Goto, NCCHE/LC-SCRUM
Screened Number of Lung Cancer with rare Driver Oncogenes and Enrollment to Cliniclal Trial in LC-SCRUM-Japan 2013/2/72015/3/6 Genetic alterations Screened No. Clinical trial Enrolled No. (%) RET fusions 34 Vandetanib (LURET) 19 (56) ROS1 fusions 61 Crizotinib (OO12-01) 26 (43) ALK fusions 23 Alectinib (J-ALEX, LOGIK1401) 3 (13) BRAF V600E mutation 6 Dabrafenib (BRF113928) 3 (50) ERBB2 mutations 9 Trastuzumab (HER2-CLHERC- B/HOT1303-B) 1 (11) Total 133 52 (39) Dr. Goto, NCCHE/LC-SCRUM
LC-SCRUM (~200 sites) GI-SCREEN (~30 sites) SCRUM-JapanDB 23 2250 2250 NCC 140 NCC
SCRUM-Japan SCRUM-Japan SCRUM-Japan SCRUM-Japan precision medicine
Super-SCRUM ELSI
proof of concept TCGA, Nature, 2014)
Multi-omics analysis re-characterized the cell lines; Multi-omics hallmarks of cancer Hallmarks of cancer (Hanahan and Weinberg. 2011 Cell) For each hallmark, we focused on aberrations in each layer of multi-omics features. Suzuki et al. 2014 Nucleic Acids Research
: Dr. D.B. Solit, MSKCC
A1 B1 C1 D1 B2 B3 B4 B5 B6 D2 D3 A2 A3 C2 C3 Hub-and-Spoke SCRUM-Japan SCRUM Incidental findings Dr. Yoshino, NCCHE/GI-SCREEN
SCRUM-Japan Acknowledgement Participating institutes and companies Tomomitsu Hotta, Atsushi Ohtsu, Koichi Goto, Takayuki Yoshino, Genta Ohno (NCC) National Cancer Center Hospital East Kiyotaka Yoh, Shigeki Umemura, Yoshitaka Zenke, Eri Sugiyama, Hibiki Udagawa, Yuki Matsumura (Fukushima Med Univ), Tomohiro Miyoshi NCCHE Office of Translational Research Tomomitsu Hotta Shimanishi President Division of TR, NCC-EPOC NCC Tomohisa Sudo, Izumi Miki, Akiko Nakayama, Junko Ikeda, Yuri Murata, Yuko Tagami, Yoriko Kato, Yumiko Shingo Matsumoto, Sachiyo Mimaki, Ayako Suzuki, Hideki Makinoshima, Koutatsu Matsushima, Sayuri Todoroki, Motoki Kasahara, Satoshi Tada (Dynacom Co. Ltd), Tomohiro Sakamoto (Tottori Univ), Hiroyasu Esumi (Tokyo Univ. Sci.), Takashi Kohno Dept. Computational Biology and Medical Sciences, The Univ. of Tokyo Yutaka Suzuki, Ken Matsui, Toshihiko Maekawa, Minoru Kubota, Sumio Sugano, Genomedia Inc. Yomoyuki Yamada, Koichiro Yamada Koichi Goto NCCHE Atsushi Ohtsu NCC EPOC Takayuki Yoshino NCCHE