Multicenter phase 2 study of taletrectinib for non-small cell lung cancer with ROS1 gene fusions

Taletrectinib is a highly potent, CNS-active, ROS1 TKI. The multicenter phase 2 TRUST-1 study in China evaluated taletrectinib for non-small cell lung cancer with ROS1 gene fusions (ROS1+ NSCLC). In TKI-naïve patients, the confirmed ORR and intracranial cORR were 91% and 88%, respectively; in crizotinib-pretreated patients, cORR and intracranial cORR were 52% and 73%. In TKI-naïve patients median duration of response and median progression-free survival were not reached with 22.1 month and 23.5 month follow-up, respectively; in crizotinib-pretreated patients these were 10.6 months (95% CI 6.3-NR) and 7.6 months (5.5-12.0). Eight of twelve patients with G2032R mutation responded. The most frequent treatment-emergent adverse event were increased AST (76% of patients), diarrhea (70%), and increased ALT (68%), most of which were grade 1-2. Incidences of neurologic TEAEs were low and mostly grade 1. Incidences of discontinuations (5%) and dose reductions (19%) due to TEAEs were low. The authors conclude that talectrinib was effacacious and safe for ROS1+ NSCLC.