NEW YORK – The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) on Thursday recommended approval for Bristol Myers Squibb's Augtyro (repotrectinib) as a treatment for patients with ROS1-positive advanced non-small cell lung cancer and for adult and pediatric patients with advanced solid tumors expressing a NTRK gene fusion.
The recommendation for ROS1-positive NSCLC was based on data from the Phase I/II TRIDENT-1 trial. In the study, 79 percent of patients who had not previously received a ROS1 tyrosine kinase inhibitor (TKI) responded to Augtyro, and the median duration of response was 34.1 months. Among patients who had prior ROS1 inhibitor treatment, 38 percent responded to Augtyro.
CHMP's recommendation for Augtyro in adult and pediatric patients 12 years of age and older with advanced solid tumors expressing a NTRK gene fusion, meanwhile, includes both patients who have received a prior NTRK inhibitor and those who have not received a prior NTRK inhibitor but for whom other treatment options not targeting NTRK have provided limited clinical benefit or have been exhausted.
The NTRK-positive solid tumor recommendation was based on several trials, including a separate cohort of NTRK fusion-positive adult patients in the TRIDENT-1 trial and the Phase I/II CARE trial in pediatric and young adult patients with solid tumors harboring ALK, ROS1, or NTRK1-3 alterations. In the NTRK-positive tumors cohort of the TRIDENT-1 trial, most patients had NTRK-positive NSCLC. In this group, NTRK TKI-naïve patients demonstrated a response rate of 62 percent and NTRK TKI pretreated patients had a response rate of 42 percent on Augtyro.
In early data from the CARE trial, presented in 2021, three of eight evaluable patients who were TKI-naïve achieved confirmed responses, including two NTRK fusion-positive solid tumors and one ROS1 fusion-positive inflammatory myofibroblastic tumor. One patient with NTRK fusion-positive sarcoma achieved stable disease out of four evaluable TKI-pretreated patients.
The European Commission will now review the CHMP recommendations in both ROS1-positive NSCLC and NTRK-positive solid tumors and is expected to issue a decision in January 2025.
The US Food and Drug Administration approved Augtyro in 2023 for the treatment of ROS1-positive advanced NSCLC. Earlier this year, the FDA also approved the drug for adult and pediatric patients 12 years and older with solid tumors harboring NTRK gene fusions.