Novel Targeted Therapy for Lung Cancer 

The FDA has approved repotrectinib for certain patients with non-small cell lung cancer harboring a ROS1 mutation or rearrangement. 

The U.S. Food and Drug Administration (FDA) has approved repotrectinib (Augtyro) for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) that harbors a mutation, fusion, or rearrangement involving the ROS1 gene. 

Repotrectinib, a type of targeted therapy called a tyrosine kinase inhibitor, is designed to inhibit mutated forms of three tyrosine kinases that can drive tumor growth: ROS1, NTRK, and ALK. Repotrectinib can block the activity of mutations in these three kinases that give cells resistance to other ROS1, NTRK, or ALK inhibitors. 

Illustration of lungs with tumors. Repotrectinib was approved to treat non-small cell lung cancer with tumors that harbor a mutation, fusion, or rearrangement involving the ROS1 gene.

The indication for this approval includes both patients who have and have not been previously treated with a ROS1 inhibitor. Repotrectinib is the first ROS1 inhibitor approved to treat patients whose tumors did not respond to or relapsed following treatment with a previous ROS1 inhibitor. 

This approval was based on data from TRIDENT-1, a phase I/II, global, multicenter, single-arm, open-label, multicohort clinical trial in which 127 patients with NSCLC harboring a ROS1 mutation, fusion, or rearrangement were evaluated after treatment with repotrectinib. Of these patients, 71 had not received a prior ROS1 inhibitor but may have received one line of immunotherapy or platinum-based chemotherapy. The remaining 56 patients had received one prior ROS1 inhibitor with no prior chemotherapy or immunotherapy. 

Patients who had not received a prior ROS1 inhibitor had an overall response rate of 79% and a median duration of response of 34.1 months. Patients who had received a prior ROS1 inhibitor had an overall response rate of 38% and a median duration of response of 14.8 months. Responses were also observed in intracranial metastases, as well as in tumors with ROS1 mutations that impart resistance to other ROS1-targeted therapies. 

NSCLC is the most common type of lung cancer. According to federal statistics, it was estimated that 238,340 individuals would be diagnosed with lung cancer and 127,070 patients would die of the disease in the United States in 2023. 

The FDA rendered its decision on November 15, 2023.