FDA Approves Repotrectinib in ROS1+ NSCLC

• Repotrectinib (Augtyro) is a new treatment option for patients with ROS1- positive advanced non–small cell lung cancer (NSCLC).
• In May 2023, the FDA granted priority review to repotrectinib for this patient population.
• The approval is supported by findings from the phase 1/2 TRIDENT-1 study (NCT03093116).

The FDA has granted approval to repotrectinib, a tyrosine kinase inhibitor (TKI), for the treatment of patients with ROS1-positive locally advanced or metastatic NSCLC.¹

Data from the phase 1/2 TRIDENT-1 study showed that patients who were TKI-naïve and TKI-pretreated, including patients who had ROS1 resistance mutations treated with repotrectinib, had a high response rate and a clinically meaningful duration of response (DOR).^2,3

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After a median follow-up of 18.1 months for the TKI-naive patients, the overall response rate (ORR) was 78.9% (95% CI, 67.6-87.7) and the 12-month landmark DOR was 86.1%. For patients who were previously treated with 1 prior ROS1 TKI and no prior chemotherapy, the ORR was 37.5% (95% CI, 24.9-51.5) with a 6-month landmark DOR of 79.5% after 15.5 months median follow up.²

“New treatment options continue to be needed for patients with ROS1 fusion-positive NSCLC that support important clinical goals, including achieving durable therapeutic responses,” said Jessica J. Lin, MD, TRIDENT-1 primary investigator and attending physician at the Center for Thoracic Cancers at Massachusetts General Hospital and Assistant Professor of Medicine at Harvard Medical School, in a 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.”¹

The median DOR was 13.3 months (range, 0.80-60.6+) in all patients treated with repotrectinib (n = 71). Among the 56 patients who achieved a complete response, the median duration of treatment was 15.5 months (range, 3.1-60.6+). Activity was also observed in pretreated patients with ROS1 G032R resistance mutation, according to investigators (ORR, 58.5%; 95% CI, 32.9-81.6).¹

For safety, repotrectinib had a tolerable safety profile. The most common treatment-emergent adverse events being low-grade dizziness (61.3%), which was grade 1 in 73.2% of patients. Additionally, 19.6% of patients had ataxia, with 20 patients (4.5%) reporting ataxia in the absence of dizziness, and 45% of patients had TEAEs leading to drug interruption, 34% had TEAEs leading to dose reductions, and 9.7% had TEAEs leading to drug discontinuation.

REFERENCES

1. US Food and Drug Administration approves Augtyro™ (repotrectinib), a next-generation Tyrosine Kinase Inhibitor (TKI), for the treatment of Locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). News release. Bristol Myers Squibb. November 15, 2023. Accessed November 16, 2023. https://tinyurl.com/hdv8h6jv

2. U.S. Food and Drug Administration accepts for priority review bristol myers squibb’s application for repotrectinib for the treatment of patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer. News release. Bristol Myers Squibb. May 30, 2023. Accessed November 13, 2023.

3. Cho BC, Lin JJ, Camidge DR, et al. Pivotal topline data from the phase 1/2 TRIDENT-1 trial of repotrectinib in patients with ROS1+ advanced non-small cell lung cancer (NSCLC). Presented at: EORTCNCI-AACR Molecular Targets and Cancer Therapeutics Symposium; http://bit.ly/3t92SyE