China’s NMPA Approves Taletrectinib in Previously Treated ROS1+ Advanced NSCLC

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China’s National Medical Products Administration (NMPA) has approved the oral, next-generation ROS1 TKI taletrectinib adipate (Dovbleron) for the treatment of adult patients with locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC) who have been previously treated with ROS1 TKIs.¹

The regulatory decision was based on 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. Findings presented at the 2024 ASCO Annual Meeting showed that in patients with advanced ROS1-positive NSCLC who received prior treatment with crizotinib (Xalkori; n = 66), taletrectinib produced a confirmed overall response rate (ORR) of 51.5% (95% CI, 38.88%-64.01%) and a disease control rate (DCR) of 83.3% (95% CI, 72.13%-91.38%).² The median time to response (TTR) was 1.4 months (95% CI, 1.38-1.41), and at a median follow-up of 9.7 months, the median duration of response (DOR) was 10.6 months (95% CI, 6.3-not reached). The median progression-free survival (PFS) was 7.6 months (95% CI, 5.5-12.0), and patients experienced a 9-month PFS rate of 47.4%.

“The treatment landscape for advanced ROS1-positive NSCLC remains challenging, especially for patients with brain metastases, who account for more than half of patients who have [experienced disease progression] following initial treatment with a ROS1 TKI, as well as those patients who develop resistance mutations,” Caicun Zhou, MD,1 PhD, director of the Department of Oncology at Shanghai East Hospital, Tongji University, stated in a news release.¹ “Taletrectinib demonstrated significant therapeutic effects on brain lesions, as well as efficacy in [patients with] crizotinib-resistant [disease]. Moreover, taletrectinib has a favorable safety profile and tolerability with low rates of dose reduction and treatment discontinuation due to adverse [effects (AEs)]. The efficacy and safety profile of taletrectinib offers a new hope for patients and I look forward to its benefit in [patients with] ROS1-positive NSCLC in China.”

Notably, a second NDA for the agent was accepted and granted priority review designation by China’s NMPA for patients with locally advanced or metastatic ROS1-positive NSCLC who have not previously been treated with ROS1 TKIs in March 2024. This NDA was supported by data from another cohort of patients treated in TRUST-I.

TRUST-1 enrolled patients at least 18 years of age with locally advanced or metastatic NSCLC harboring a ROS1 fusion.² Patients needed to have an ECOG performance status of 0 or 1.

Patients were divided into 2 cohorts. Cohort A included patients naive to a ROS1 TKI, and cohort B featured patients who were previously treated with crizotinib. Patients in both cohorts received taletrectinib at 600 mg once per day.

Confirmed ORR per RECIST 1.1 criteria as assessed by an independent review committee served as the trial’s primary end point. Secondary end points included DOR, intracranial ORR, best overall response, DCR, TTR, PFS, and safety.

In the United States, taletrectinib was granted orphan drug designation by the FDA for the treatment of patients with ROS1-positive NSCLC and other NSCLC indications.¹ The agent also received a breakthrough therapy designation by both the United States FDA and China’s NMPA for patients with locally advanced or metastatic ROS1-positive NSCLC.

“The approval of taletrectinib is a reflection of its potential best-in-class efficacy and safety profile, as demonstrated in the TRUST-I trial,” Hui Zhou, PhD, senior vice president of Innovent, stated in a news release. “We are delighted about the approval of taletrectinib and will bring this precision therapy to patients [with NSCLC] who need novel treatment options. Innovent’s robust TKI product pipeline…showcases our leadership and synergistic strengths in precision oncology. We endeavor to advance more innovative medicines to enhance patients' quality of life.”

References

1. Innovent receives approval of Dovbleron (taletrectinib adipate capsule, ROS1 inhibitor) by China’s National Medical Products Administration. News release. Innovent. December 20, 2024. Accessed December 20, 2024. https://www.innoventbio.com/InvestorsAndMedia/PressReleaseDetail?key=498
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(suppl 16):8520. doi:10.1200/JCO.2024.42.16_suppl.8520