FDA Grants Taletrectinib Priority Review in ROS1+ Advanced NSCLC

• The FDA has granted priority review to the new drug application (NDA) for taletrectinib, a treatment for patients with ROS1-positive advanced non–small cell lung cancer (NSCLC).
• This review follows promising data from 2 pivotal phase 2 trials, TRUST-1 (NCT04395677) and TRUST-II (NCT04919811).
• A target action data of June 23, 2025, under the prescription drug user fee act, has been set.

The FDA has granted priority review to the NDA seeking the approval of taletrectinib (AB-106) for the treatment of patients with ROS1-positive advanced NSCLC.¹

Data from a pooled analysis of the phase 2 TRUST-1 (NCT04395677) and TRUST-II (NCT04919811) trials presented at the 2024 ESMO Congress support this review. Here, taletrectinib led to a confirmed overall response rate (ORR) of 88.8% (95% CI, 82.8%-93.2%) among treatment-naive patients (n = 160).² In those previously treated with a ROS1 tyrosine kinase inhibitor (TKI; n = 113), the confirmed ORR was 55.8%. Notably, patients with the ROS1 G2032R mutation (n = 13) within the previously treated cohort achieved a 61.5% confirmed ORR.

The trials enrolled adult patients with locally advanced or metastatic ROS1-positive NSCLC, including those with stable central nervous system (CNS) involvement. All patients received taletrectinib at a dose of 600 mg once daily.

“We are thrilled to reach this important milestone for taletrectinib, a significant step forward for people living with ROS1-positive NSCLC who urgently need new treatment options,” said David Hung, MD, founder, president, and chief executive officer of Nuvation Bio, in a press release.¹ “With data from over 300 patients—the largest ROS1-positive NSCLC dataset to date supporting an original NDA—taletrectinib has demonstrated the potential to deliver durable and meaningful benefits.”

Additional results from the TKI-naive cohort showed that at a median follow-up of 21.2 months (range, 3.6-46.6), the median progression-free survival (PFS) was 45.6 months (95% CI, 29.0-not reached [NR]), and the median duration of response (DOR) was 44.2 months (95% CI, 30.4-NR). For CNS activity, the intracranial ORR (IC-ORR) was 76.5% among evaluable patients (95% CI, 50.1%-93.2%). In the TKI-pretreated cohort at a median follow-up of 21.0 months (range, 3.9-45.4), the median PFS was 9.7 months (95% CI, 7.4-12.0), and the median DOR was 16.6 months (95% CI, 10.6-27.3). The confirmed IC-ORR in this group of 32 evaluable patients was 65.6% (95% CI, 46.8%-81.4%).

In terms of safety, the treatment showed a high incidence of treatment-emergent adverse events (TEAEs). Among evaluable patients, 99.7% experienced any-grade TEAEs, and 51.6% had grade 3 or higher TEAEs. Common AEs also included liver enzyme elevations (aspartate aminotransferase 72.1%, alanine aminotransferase 68%), diarrhea (63.2%), and nausea (47.2%). Further, TEAEs led to dose reductions and treatment discontinuation in 28.8% and 6.5% of patients, respectively.

The NDA is now under review by the FDA, with a target decision date set for June 23, 2025.

REFERENCES:

1. U.S. Food and Drug Administration accepts for priority review Nuvation Bio’s new drug application for taletrectinib for the treatment of advanced ROS1-positive non-small cell lung cancer. News release. Nuvation Bio. December 23, 2024. Accessed December 23, 2024. https://tinyurl.com/2wn48da4

2. Pérol M, Li W, Pennell NA, et al. Pooled efficacy and safety from 2 pivotal phase II trials of taletrectinib in patients (pts) with advanced or metastatic ROS1+ non-small cell lung cancer (NSCLC). Ann Oncol. 2024;35(suppl 2):S821. doi:10.1016/j.annonc.2024.08.1346