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

Illustration of human lungs: © Mopic - stock.adobe.com

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. https://tinyurl.com/bdeabb6d

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