FDA to Conduct Swift Review of the NDA for Repotrectinib in ROS1+ Advanced NSCLC


Results from TRIDENT-1 are supporting a new drug application for repotrectinib, a potential treatment for ROS1-positive advanced non–small cell lung cancer.

  • The new drug application (NDA) for repotrectinib (TPX-0005) for the treatment of ROS1-positive, locally advanced/metastatic non–small cell lung cancer (NSCLC) has been accepted by the FDA.

  • The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of November 27, 2023, for the NDA.

  • The NDA is supported by findings from the phase 1/2 TRIDENT-1 study (NCT03093116).

The FDA has granted priority review to the tyrosine kinase inhibitor (TKI), repotrectinib (TPX-0005) for the treatment of patients with ROS1-positive locally advanced or metastatic NSCLC.1

“Patients with ROS1-positive non–small cell lung cancer face a rare disease with a significant unmet medical need given the limited durability of benefit and emergence of resistance to approved therapies,” said Jonathan Cheng, MD, senior vice president and head of oncology development, Bristol Myers Squibb, in a press release.

In the phase 1/2 TRIDENT-1 study, repotrectinib achieved ahigh response rate as well as clinically meaningful duration of response (DOR) in patients who were TKI-naïve and TKI-pretreated, including patients who had ROS1 resistance mutations.1,2

In TKI-naïve patients, after a median follow up of 18.1 months, ORR was 78.9% (95% CI, 67.6-87.7) and 12-month landmark DOR was 86.1%. Patients pretreated with one prior ROS1 TKI and no prior chemotherapy demonstrated an ORR of 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

In all patients treated with repotrectinib in the study (n = 71), the median DOR was 13.3 months (range, 0.80-60.6+). In all patients who achieved a CR (n = 56), the median duration of treatment was 15.5 months (range, 3.1-60.6+).

Repotrectinib also demonstrated a tolerable safety profile in the TRIDENT-1 study with the most common treatment-emergent adverse events being low-grade dizziness (61.3%), which was grade 1 in 73.2% of patients.

“The FDA’s acceptance of this application marks an exciting milestone on our journey to bring this next-generation tyrosine kinase inhibitor to patients. If approved, this would represent a potential best-in-class option for TKI-naïve patients and a potential first-in-class option for patients with ROS1-positive NSCLC who have been previously treated with TKI, and for whom there are currently no approved targeted therapies available. We are eager to continue working closely with the FDA on the review of this precision medicine, which has shown unprecedented level of durability of responses and robust intracranial responses in patients with ROS1-positive NSCLC,” said Cheng, in a press release.1


1. 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 May 30, 2023. https://shorturl.at/axFY9

2. 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

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