On November 15, 2023, the U.S. FDA approved the oral tyrosine kinase inhibitor (TKI) Augtyro (repotrectinib) for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). Developed by Bristol-Myers Squibb, Repotrectinib is the first next-generation TKI therapy approved for ROS1-positive NSCLC patients. Data shows that Repotrectinib resulted in significant tumor shrinkage in up to 79% of patients, with an average duration of response of 34.1 months, and the drug demonstrated a good safety profile.
Clinical data：
The approval is based on TRIDENT-1, a global, multicenter, single-arm, open-label, multi-stake clinical trial (NCT03093116) that included patients with ROS1-positive locally advanced or metastatic NSCLC. Efficacy was evaluated in 71 ROS1 TKI-naïve patients who had received up to one line of platinum-based chemotherapy and/or immunotherapy, and in 56 patients who had received one prior line of ROS1 TKI therapy but had not previously received platinum-based chemotherapy or immunotherapy.
According to RECIST v1.1, the primary efficacy outcome measures were overall response rate (ORR) and duration of response (DOR), assessed by blinded independent central evaluation. In patients previously treated with ROS1 inhibitors, the confirmed ORR in the ROS1 TKI-naïve group was 79% (95% CI: 68, 88) and 38% (95% CI: 25, 52), respectively. The median DOR in the two groups was 34.1 months (95% CI: 25.6, non-evaluable) and 14.8 months (95% CI: 7.6, non-evaluable), respectively. Responses were observed in patients with measurable central nervous system metastases and in patients with resistance mutations following TKI treatment.
Adverse reactions
① In the TRIDENT-1 trial, among 351 patients with ROS1-positive NSCLC and other solid tumors who received AUGTYRO, the most common adverse reactions (>20%) were dizziness (64%), taste disturbance (50%), peripheral neuropathy (47%), constipation (37%), dyspnea (30%), ataxia (29%), fatigue (29%), cognitive impairment (23%), and nausea (20%).
② Among the 264 patients with ROS1-positive NSCLC who received AUGTYRO treatment, the most common adverse reactions (≥20%) were dizziness (63%), taste disturbance (48%), peripheral neuropathy (47%), constipation (36%), dyspnea (30%), ataxia (28%), fatigue (24%), cognitive impairment (23%), and muscle weakness (21%).
Dosage
The recommended dose of repotrectinib is 160 mg orally once daily, with or without food, for 14 days, then increased to 160 mg twice daily until disease progression or unacceptable toxicity occurs.
