FDA D.I.S.C.O. Burst Edition: FDA approval of Augtyro (repotrectinib) for locally advanced or metastatic ROS1-positive non-small cell lung cancer
Regulatory approval: On Nov 15, 2023, the FDA approved repotrectinib (Augtyro) for locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). The approval includes patients who are ROS1 tyrosine kinase inhibitor (TKI)–naïve and those previously treated with a ROS1 TKI. The decision was based on the single-arm TRIDENT-1 trial, with confirmed ORR 79% in TKI-naïve patients and 38% after a prior ROS1 inhibitor; median duration of response was 34.1 and 14.8 months, respectively.
FDA approval (regulatory news)
On Nov 15, 2023, the FDA approved repotrectinib (Augtyro) for locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).
According to the FDA, this is the first FDA approval in ROS1-positive NSCLC that includes patients previously treated with a ROS1 tyrosine kinase inhibitor (TKI), in addition to TKI-naïve patients.
Supporting evidence
Approval was based on TRIDENT-1, a global, multicenter, single-arm, open-label, multi-cohort clinical trial in patients with ROS1-positive locally advanced or metastatic NSCLC.
Efficacy was evaluated in:
- 71 ROS1 TKI–naïve patients who received up to 1 prior line of platinum-based chemotherapy and/or immunotherapy
- 56 patients who had received 1 prior ROS1 TKI and had no prior platinum-based chemotherapy or immunotherapy
Major endpoints were overall response rate (ORR) and duration of response (DOR) per RECIST v1.1 by blinded independent central review. Confirmed ORR was 79% in the TKI-naïve group and 38% in patients previously treated with a ROS1 inhibitor. Median DOR was 34.1 months and 14.8 months, respectively. Responses were reported in intracranial lesions in patients with measurable CNS metastases and in patients with resistance mutations after TKI therapy.
Safety
Most common adverse reactions (>20%) were dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive disorders, and muscular weakness.