ISY2-1 - Activity on the Nationwide Cancer Genome Screening Project for Gastrointestinal Cancer in Japan; SCRUM-Japan GI-SCREEN

Abstract

Several cancer genome alterations have been identified as important targets for cancer treatment, which include BRAF mutation, HER-2 overexpression/amplification, Microsatellite Instability-High (MSI-High), and ALK, ROS1, NTRK fusion in metastatic colorectal cancer (mCRC), for which corresponding targeting INDs showed attractive activity in early clinical trials. More recently, in order to overcome an acquired resistance mechanism to anti-EGFR therapy in RAS/BRAF/PI3KCA wild type mCRC patients, the innovative challenge has been initiated in patients with mCRC harboring identified acquired targets such as RAS mutations, HER-2 overexpression/amplification and c-MET amplification by means of NGS- and blood-based molecular testing using cell -free tumor DNA. In addition, emerging concept in clinical development targeting Microsatellite stable (MSS) mCRC comes into question which compound adding on an immune checkpoint inhibitor evokes immunity. We initiated the Nationwide Cancer Genome Screening Project in Japan (GI-SCREEN) in February 2014 to detect rare mutations from CRC. Current clinical development of corresponding INDs in molecularly characterized cohorts of mCRC patients as well as in acquired targets by means of NGS- and blood-based molecular testing may represent more substantial progress toward the Precision Medicine. Accordingly, efficient screening systems for these relatively minor cancer genome alterations are necessary for the successful development of targeted therapies. Furthermore, successful combination strategy evoking immunity for MSS mCRC will break out of the paradigm in terms of the treatment strategy in mCRC. Updated activities in SCRUM-Japan GI-SCREEN will be presented.