FDA Granted Breakthrough Therapy Designation to Taletrectinib for ROS1+ NSCLC

The FDA has granted breakthrough therapy designation to the ROS1 inhibitor taletrectinib for the treatment of patients with advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC) who are naïve to treatment with ROS1 tyrosine kinase inhibitors (TKI) or who were previously treated with crizotinib. This breakthrough therapy designation was supported by data from an ongoing phase 2 trial (TRUST) in Chinese ROS1-positive NSCLC patients and two completed Phase 1 clinical trials conducted in the United States and Japan.

The confirmed objective response rate (cORR) and disease control rate (DCR) of 67 evaluable ROS1 TKI-naïve patients with ROS1 fusion-positive NSCLC was 92.5% and 95.5%, respectively. While for 38 evaluable crizotinib-pretreated patients, the cORR and DCR was 50% and 78.9%, respectively.

Taletrectinib is a novel and potential best-in-class next-generation ROS1 inhibitor. It is designed to target ROS1 fusions effectively with the potential to treat both TKI-naïve and pre-treated patients. ROS1 rearrangement is estimated to be an oncogenic driver in approximately 1 to 2 percent of patients with NSCLC. ROS1 fusions are also observed in several other cancers such as cholangiocarcinoma, glioblastoma, ovarian, gastric, and colorectal cancers. Moreover, taletrectinib has demonstrated excellent potency against crizotinib resistance, good brain penetration and intracranial antitumor activity, and favorable safety profiles in ROS1 fusion-positive NSCLC patients.