Taletrectinib Approved in China for Locally Advanced/Metastatic ROS1+ NSCLC

The National Medical Products Administration (NMPA) of China has approved taletrectinib adipate capsule (Dovbleron), a next-generation ROS1 TKI, for the treatment of adult patients with locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC).1

This regulatory decision was supported by findings from the multicenter, open-label, single-arm phase 2 TRUST-I trial (NCT04395677), which investigated taletrectinib in Chinese patients with advanced ROS1-positive NSCLC. These findings were presented at the 2024 ASCO Annual Meeting and published in the Journal of Clinical Oncology.

“We are glad to see that [taletrectinib] has been approved for ROS1-positive NSCLC across treatment lines at a fast pace,” Caicun Zhou, MD, PhD, of the Department of Oncology at Shanghai East Hospital of Tongji University in China, stated in a news release. “[Taletrectinib] demonstrated superior efficacy compared with the first-generation TKIs. These TRUST-I results reinforce taletrectinib’s high overall response [rate (ORR)] and prolonged progression-free survival [PFS]. The efficacy and safety profile of [taletrectinib] offers a more effective first-line treatment option, and I look forward to its benefit [for patients with] ROS1-positive NSCLC in China.”

In TRUST-I, patients at least 18 years of age with locally advanced or metastatic NSCLC, an ECOG performance status of 0 or 1, and evidence of a ROS1 fusion in tumor tissue received taletrectinib at 600 mg daily.2 Independent review committee (IRC)–assessed confirmed ORR per RECIST 1.1 criteria served as the primary end point. Secondary end points included duration of response (DOR), intracranial ORR (IC-ORR), best overall response, disease control rate (DCR), time to response (TTR), PFS, and safety.

Among 106 patients with ROS1 TKI–naive NSCLC, the confirmed ORR per IRC was 90.6% (95% CI, 83.33%-95.38%). The DCR was 95.3% (95% CI, 89.33%-98.45%), and the median TTR was 1.4 months (95% CI, 1.38-1.41). At a median follow-up of 23.5 months, the median DOR and PFS per IRC assessment were both not yet reached, and the respective 24-month DOR and PFS rates were 78.6% and 70.5%.

Among TKI-naive patients with measurable baseline brain metastases (n = 8), the confirmed IC-ORR was 87.5% (95% CI, 47.35%-99.68%), and the DCR was 100.0% (95% CI, 63.06%-100.0%).

Among all patients enrolled in TRUST-I (n = 173), treatment-emergent adverse effects (TEAEs) led to treatment interruption, dose reduction, or treatment discontinuation in 40.5%, 19.1%, and 5.2% of patients, respectively. Trial investigators noted that the rates of neurologic TEAEs were low and mostly grade 1. These included any-grade dizziness (23.1%) and any-grade dysgeusia (10%).

In December 2024, the NMPA approved taletrectinib in China for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC who had received prior treatment with ROS1 TKIs.1

“The [approval of] 2 new drug applications [for taletrectinib] is a reflection of its potential best-in-class efficacy to fulfill the urgent need of patients with ROS1-positive NSCLC,” Hui Zhou, PhD, senior vice president of Innovent Biologics, added in the news release. “We recently launched the first batch of [taletrectinib] to market, rapidly bringing this precision therapy to [patients with] NSCLC who need novel treatment options. Innovent’s robust TKI product pipeline—including [selpercatinib (Retsevmo)], [pemigatinib (Pemazyre)], [fulzerasib (Dupert)], and [taletrectinib]—showcases our leadership and synergistic strengths in precision oncology. We endeavor to advance more innovative medicines to enhance patients’ quality of life.”

Previously, taletrectinib received orphan drug designation from the FDA for the treatment of patients with ROS1-positive NSCLC. The agent has also received breakthrough therapy designations from the FDA and the NMPA for the treatment of patients with locally advanced or metastatic ROS1-positive NSCLC. In December 2024, the FDA also granted priority review to an NDA for taletrectinib for the line-agnostic treatment of patients with advanced ROS1-positive NSCLC. The NDA was based on pooled findings from the TRUST-I and phase 2 TRUST-II (NCT04919811) trials.

References

1. Innovent announces second new drug application of Dovbleron (taletrectinib adipate capsule, ROS1 inhibitor) was approved by China's National Medical Products Administration. News release. Innovent Biologics, Inc. January 3, 2025. Accessed January 3, 2025. https://www.innoventbio.com/InvestorsAndMedia/PressReleaseDetail?key=500
2. Li W, Xiong A, Yang N, et al. Efficacy and safety of taletrectinib in patients with advanced or metastatic ROS1+ non–small cell lung cancer: the phase 2 TRUST-I study. J Clin Oncol. 2024;42(22):2660-2670. doi:10.1200/JCO.24.00731