Data from the phase 1/2 TRIDENT-1 trial support the FDA approval of repotrectinib for those with ROS1-positive advanced or metastatic non–small cell lung cancer.
The FDA has granted approval to repotrectinib (Augtyro) as a therapy for patients with locally advanced or metastatic ROS1 positive non–small cell lung cancer (NSCLC), according to a press release from Bristol Myers Squibb.1
Supporting data for the approval of repotrectinib in this indication came from the multi-center, open-label phase 1/2 TRIDENT-1 trial (NCT03093116), in which investigators assessed the safety and anti-tumor activity of repotrectinib among patients with advanced solid tumors with ROS1 fusions, including those with NSCLC. Among 71 patients who were naïve to treatment with tyrosine kinase inhibitors (TKIs), repotrectinib elicited an objective response rate (ORR) of 79% (95% CI, 68%-88%) and a median duration of response (DOR) of 34.1 months.
Of 56 patients who previously received a ROS1 TKI but no chemotherapy, an objective response was achieved in 38% (95% CI, 25%-52%). Additionally, the median DOR was 14.8 months in this population.
Among patients with evaluable central nervous system metastases, investigators observed an intracranial response with repotrectinib in 7 of 8 patients who were naïve to TKIs. Moreover, 5 of 12 patients previously treated with TKIs experienced responses in intracranial lesions.
“New treatment options continue to be needed for patients with ROS1 fusion-positive NSCLC that support important clinical goals, including achieving durable therapeutic responses,” lead study investigator Jessica J. Lin, MD, attending physician at the Center for Thoracic Cancers at Massachusetts General Hospital and assistant professor of Medicine at Harvard Medical School, said in the press release. “Based on the data we have seen in the TRIDENT-1 trial, repotrectinib has the potential to become a new standard of care option for patients with locally advanced or metastatic ROS1 fusion-positive lung cancer.”
Based on findings from the TRIDENT-1 trial, the FDA approved administering repotrectinib at 160 mg orally once a day for 2 weeks followed by 160 mg twice a day until progressive disease or unacceptable toxicity.
The trial’s primary end points were dose-limiting toxicities and the recommended phase 2 dose during phase 1 as well as ORR in phase 2. Key secondary end points included DOR per RECIST v1.1 criteria, progression-free survival, and intracranial responses.
Investigators reported treatment discontinuation of repotrectinib in 8% of the TRIDENT-1 population. Dose interruptions and dose reductions, respectively, occurred in 48% and 35% due to adverse effects (AEs). The most frequent any-grade AEs included dizziness (63%), dysgeusia (48%), peripheral neuropathy (47%), constipation (36%), dyspnea (30%), ataxia (28%), fatigue (24%), cognitive disorders (23%), and muscular weakness (21%).
Overall, 33% of patients in the study experienced serious AEs. The most common toxicities of this kind included pneumonia (5.7%), dyspnea (3.8%), pleural effusion (3.4%), and hypoxia (3.0%). Investigators reported AEs leading to death in 4.2% of the population.
The FDA previously granted priority review to repotrectinib as a treatment for ROS1-positive advanced or metastatic NSCLC in May 2023.2