A Study of LDK378 in Patients With Non-small Cell Lung Cancer Harboring ROS1 Rearrangement

Recently, our group found the prevalence of ROS1 rearrangement reached up to 3.2% in clinically selected population (never smokers) and 5% in genetically selected population (EGFR-/ALK-wild-type). These data strongly suggests that ROS1 rearrangement is a potential therapeutic target with relatively high incidence. In this study, investigator confirmed the presence of ROS1 fusion by RT-PCR and correlation between FISH and IHC (Cell Signaling Technology®). LDK378 is an orally highly selective and potent ALK kinase inhibitor. In preclinical studies, LDK378 has much lower IC50 values than crizotinib in cell lines engineered to express ROS1 rearrangement (0.15 nM versus 3 nM) and is approximately 20-fold more potent. LDK378 is a potent inhibitor of tumor growth in rodent models of both ALCL and NSCLC. Investigators suggest a phase II trial of LDK378 in advanced non-small cell lung cancer patients with ROS1 rearrangement. The aim of current trial is to evaluate the antitumor efficacy and safety profile of LDK378.