FDA Grants Priority Review to Taletrectinib in ROS1+ Advanced NSCLC

FDA

The FDA has granted priority review to the new drug application (NDA) seeking the approval of taletrectinib for the treatment of patients with ROS1-positive advanced non–small cell lung cancer.¹

The NDA is supported by data from a pooled analysis of the phase 2 TRUST-1 (NCT04395677) and TRUST-II (NCT04919811) trials. Findings presented at the 2024 ESMO Congress showed that taletrectinib generated a confirmed overall response rate (ORR) of 88.8% (95% CI, 82.8%-93.2%) in patients with ROS1-positive advanced NSCLC who were naive to a ROS1 TKI (n = 160).² Patients who were previously treated with a ROS1 TKI (n = 113) experienced a confirmed ORR of 55.8% (95% CI, 46.1%-65.1%). Within the previously treated cohort, patients harboring ROS1 G2032R mutations (n = 13) achieved a confirmed ORR of 61.5% (95% CI, 31.6%-86.1%).

The FDA assigned a target action data of June 23, 2025, under the prescription drug user fee act.¹

“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,” David Hung, MD, founder, president, and chief executive officer of Nuvation Bio, stated in a news release. “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.”

TRUST-I was a multicenter, open-label, single-arm trial conducted in China, and TRUST-II was a global, multicenter, open-label, single-arm study.² The pivotal cohorts included patients at least 18 years of age with locally advanced or metastatic NSCLC harboring a ROS1 fusion. Patients with stable central nervous system involvement were allowed to enroll. Other key inclusion criteria consisted of an ECOG performance status of 0 or 1 and at least 1 measurable lesion per RECIST 1.1 criteria.

Patients were split into cohorts based on prior exposure to a ROS1 TKI. All patients received taletrectinib at 600 mg once per day. Notably, 3 patients treated in TRUST-1 received the agent at a starting dose of 400 mg once per day, and 2 of these patients escalated to 600 mg per day.

Confirmed ORR per RECIST 1.1 criteria as assessed by independent review committee served as the trials’ primary end point. Secondary end points included confirmed intracranial ORR (IC-ORR) per modified RECIST 1.1 criteria, progression-free survival (PFS), duration of response (DOR), and safety.

Additional data from the TKI-naive cohort showed that at a median follow-up of 21.2 months (range, 3.6-46.6), the median PFS was 45.6 months (95% CI, 29.0-not reached [NR]), and the median DOR was 44.2 months (95% CI, 30.4-NR). Among evaluable patients (n = 17), the confirmed IC-ORR was 76.5% (95% CI, 50.1%-93.2%).

At a median follow-up of 21.0 months (range, 3.9-45.4) in the TKI-pretreated cohort, 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 was 65.6% (95% CI, 46.8%-81.4%) among evaluable patients (n = 32).

Safety data for evaluable patients with ROS1-positive NSCLC treated with taletrectinib at 600 mg per day (n = 337) showed the rates of any-grade treatment-emergent adverse effects (TEAEs) and grade 3 or higher TEAEs were 99.7% and 51.6%, respectively. The most common TEAEs reported in at least 15% of patients included increased aspartate aminotransferase levels (any-grade, 72.1%; grade ≥ 3, 7.7%), increased alanine aminotransferase levels (68.0%; 10.1%), diarrhea (63.2%; 2.1%), nausea (47.2%; 1.5%), vomiting (43.3%; 1.5%), anemia (37.4%; 3.6%), constipation (21.1%; 0%), QT prolongation (19.3%; 3.6%), increased blood creatinine levels (18.1%; 0%), increased blood creatine phosphokinase levels (16.6%; 2.1%), decreased neutrophil counts (16.6%; 4.2%), decreased appetite (15.7%; 0.3%), and decreased white blood cell counts (15.7%; 1.5%).

TEAEs led to dose reductions and treatment discontinuation in 28.8% and 6.5% of patients, respectively.

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://investors.nuvationbio.com/news/news-details/2024/U.S.-Food-and-Drug-Administration-Accepts-for-Priority-Review-Nuvation-Bios-New-Drug-Application-for-Taletrectinib-for-the-Treatment-of-Advanced-ROS1-positive-Non-Small-Cell-Lung-Cancer/default.aspx
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