ROS1 and pan-NTRK inhibitor for NSCLC resistant to Xalkori

INDICATION: Non-small cell lung cancer (NSCLC)

A dual ROS1 and pan-NTRK inhibitor from Daiichi Sankyo Co. Ltd. could treat Xalkori crizotinib-resistant NSCLC, which has been linked to ROS1 mutations. In vitro high throughput screening for ROS1 inhibitors followed by optimization of a hit that inhibited ROS1 and NTRK kinases yielded DS-6051b. In three patient-derived ROS1 fusion-positive NSCLC cell lines, DS-6051b inhibited proliferation with IC₅₀ values of about 7-25 nM and more potently than Xalkori, for which the IC₅₀ was 15-100 nM. Additionally, DS-6051B reduced tumor growth in mice with ROS1 G2032R-mutant NSCLC resistant to Xalkori...