Clini Cancer Research: Second generation ROS1-TKI, repotrectinib, anti-tumor activity of NSCLC for primary treatment or ROS1 mutation

Objective: Although the treatment of first-line keratosin has benefited patients with ROS1 and lung cancer, the incidence of ROS1-G2032R (ROS1G2032R) mutation and the progress of the central nervous system (CNS) pose challenges to the treatment of lung cancerThis study is intended to evaluate the anti-tumor activity of a new type of second-generation ROS1/TRK/ALK tyrosine kinase inhibitor (TKI) repotrectinib for preclinical models of ROS1-patient sourcesdesign: evaluating the anti-tumor activity of repotrectinib in preclinical models of THE SOURCE of ROS1 plus mutation patients (including primary treatment and ROS1G2032R models) and further validated in patients recruited in an ongoing Phase I/II clinical trial (NCT03093116)The intracranial antitumor activity of repotrectinib was evaluated in the mouse model of brain metastasisresults: compared to the clinically available grameini, seritinib and ntutinib, repotrectinib can effectively inhibit the growth of invivial tumors and the downstream signal of ROS1 in the initial treatment of THE YU1078 modelAlthough tumor regression in the heterotransplant model of the YU1078 source from repotrectinib and Laura Tini was comparable, repotrectinib significantly delayed the recurrence of the tumor after discontinuationIn addition, repotrectinib can effectively cross the blood-brain barrier and play significant anti-tumor activity in CNSIt is worth noting that repotrectinib exhibited selective and strong activity in both in vitro and in vivo for the ROS1G2032R mutationThese results have been validated in ongoing Phase I/II clinical trialsconclusion: Repotrectinib is a new generation of ROS1-TKI, which has better anti-tumor activity and selectivity for lung cancer with primary treatment and ROS1G2032R mutation, and can effectively penetrate the blood-brain barrierThe results of this study suggest that repotrectinib can be used effectively as a first-line therapy forNSCLCand a rescue therapy for progression after the treatment of ROS1-TKI