The Food and Drug Administration (FDA) has accepted a new drug application (NDA) with priority review for the investigational next-generation ROS1 tyrosine kinase inhibitor (TKI) taletrectinib in the treatment of advanced ROS1-positive non–small cell lung cancer (NSCLC), according to a news release from Nuvation Bio Inc. Notably, the application has a Prescription Drug User Fee Act (PDUFA) action date of June 23, 2025.
The NDA is based on the pooled results from the pivotal phase 2 TRUST-I clinical trial, which was conducted in China, as well as the TRUST-II global study, both of which investigated taletrectinib. Data on the agent were shared at the 2024 ESMO Congress in September.
“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 Dr. David Hung, founder, president and chief executive officer of Nuvation Bio, in the 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.”
Diving Into the TRUST-I and TRUST-II Clinical Trials
The phase 2 clinical trials evaluated the ROS1 TKI in 337 patients with advanced ROS1-positive NSCLC. These patients received taletrectinib at a dose of 600 mg orally once daily in 21-day cycles. The primary end point of these studies is confirmed objective response rate (cORR) as assessed by an independent review committee, while key secondary end points include intracranial cORR, duration of response (DOR), progression-free survival (PFS) and safety.
In the data shared at the ESMO Congress, investigators noted that in patients with advanced ROS1-positive NSCLC who were TKI-naive and in patients who were TKI-pretreated, tumors shrank in 89% and 56% of patients, respectively. Furthermore, the agent demonstrated durable responses and prolonged PFS. The median DOR was 44 months in TKI-naive patients and the median PFS was 46 months in the same patient group. Additionally, the agent had a favorable safety and tolerability profile.
More Information on the Use of Taletrectinib
More than one million people globally are diagnosed with NSCLC every year, and approximately 2% of those have ROS1-positive mutations. Of these patients, 35% have tumors that spread to their brain, which increases to 55% for those whose cancer has progressed following first-line treatment, according to the news release. In turn, this creates an unmet need for patients. The news release notes that this priority review designation of taletrectinib underscores the advancements that the agent may offer for this patient population.
Taletrectinib, which is an oral, potent, central nervous system-active, selective agent, previously received orphan drug designation from the FDA and is currently the only ROS1 TKI in development that has received breakthrough therapy designation from the FDA for the treatment of patients with locally advanced or metastatic ROS1-positive NSCLC.
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