On November 15, 2023, repotrectinib (Augtyro) was approved for locally advanced or metastatic ROS1 fusion–positive non–small cell lung cancer (NSCLC).1 This is the first U.S. Food and Drug Administration approval that includes patients with ROS1-positive NSCLC who have previously received a ROS1 tyrosine kinase inhibitor and those who are tyrosine kinase inhibitor–naive.
Supporting Efficacy Data
Approval was based on the multicenter multicohort TRIDENT-1 trial (ClinicalTrials.gov identifier NCT03093116), including 71 ROS1 tyrosine kinase inhibitor–naive patients who received up to one prior line of platinum-based chemotherapy and/or immunotherapy and 56 patients who received one prior ROS1 tyrosine kinase inhibitor with no prior platinum-based chemotherapy or immunotherapy. Patients received oral repotrectinib at 160 mg once daily for 14 days and then at 160 mg twice daily until disease progression or unacceptable toxicity.
The objective response rates on blinded independent central review were 79% (95% confidence interval [CI] = 68%–88%) in the ROS1 tyrosine kinase inhibitor–naive group and 38% (95% CI = 25%–52%) in the group with prior ROS1 tyrosine kinase inhibitor treatment. The median durations of response were 34.1 months (95% CI = 25.6 months to not evaluable) and 14.8 months (95% CI = 7.6 months to not evaluable). Response ranges were at least 1.4 months to 42.4 months or more and 3.6 months to 22.9 months or more, respectively; proportions of responses lasting at least 12 months were 70% and 48%, respectively.
How It Is Used
The recommended repotrectinib dose is 160 mg once daily for 14 days, followed by 160 mg twice daily until disease progression or unacceptable toxicity. Product labeling provides instructions on dosage modification for adverse reactions.
Safety Profile
Among 264 patients with ROS1-positive NSCLC who received repotrectinib in TRIDENT-1, the most common adverse events of any grade were dizziness (63%), dysgeusia (48%), peripheral neuropathy (47%), constipation (36%), dyspnea (30%), ataxia (28%), fatigue (24%), cognitive disorders (23%), and muscular weakness (21%). The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes (10%), hemoglobin (5%), and leukocytes (4.7%).
OF NOTE
Repotrectinib has warnings/precautions for central nervous system effects, interstitial lung disease/pneumonitis, hepatotoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, skeletal fractures, and embryofetal toxicity.
Repotrectinib has warnings/precautions for central nervous system effects, interstitial lung disease/pneumonitis, hepatotoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, skeletal fractures, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving repotrectinib.
REFERENCE
1. Augtyro (repotrectinib) capsules, for oral use, prescribing information, Turning Point Therapeutics, Inc, a Bristol Myers Squibb company, November 2023. Available at Augtyrohcp.com. Accessed December 7, 2023.
