Taletrectinib Gains Chinese Approval for Advanced ROS1-Positive NSCLC

The decision is supported by results from the phase 2 TRUST-1 trial, which evaluated the safety and efficacy of taletrectinib in ROS1-positive NSCLC.

China’s National Medical Products Administration (NMPA) has approved the new drug application (NDA) of taletrectinib (Dovbleron) as a treatment for adult patients with locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC), according to a news release from the drug’s developer, Innovent Biologics.¹

The approval decision was supported by findings from the phase 2 TRUST-1 trial (NCT04395677), which evaluated the safety and efficacy of taletrectinib in patients with ROS1-positive disease in China. Efficacy results published in the Journal of Clinical Oncology reveal that among 106 patients who were naïve to treatment with tyrosine kinase inhibitors (TKIs), the confirmed overall response (cORR) assessed by independent review committee (IRC) was 90.6% (95% CI, 83.33%-95.38%).² Furthermore, 4 patients (3.8%) in the TKI-naïve group achieved a complete response (CR), and 92 (86.8%) achieved a partial response (PR).

“We are glad to see that [taletrectinib] has been approved for ROS1-positive NSCLC across treatment lines at a fast pace. [Taletrectinib] demonstrated superior efficacy compared to the first-generation TKIs,” senior study author Caicun Zhou, MD, PhD, director of the department of Oncology at Shanghai East Hosptial, Tongji University, said in the news release on the approval.¹ “These TRUST-I results reinforce taletrectinib's high overall response 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 in the [patients with] ROS1-positive NSCLC in China."

Investigators of the phase 2, multicenter, single-arm TRUST-1 study initially conducted a safety lead-in stage to evaluate the safety, tolerability, and pharmacokinetics of taletrectinib in 6 patients at 2 dose levels: 400 mg and 600 mg both once daily. Three patients were treated at the 400 mg dose, with 2 escalating to the 600 mg dose level.

The recommended phase 2 dose of 600 mg once daily was confirmed during the safety lead-in. All study patients were treated with this regimen in 21-day treatment cycles.

As of the data cutoff point of November 29, 2023, 173 patients were enrolled on study, 106 of whom were TKI-naïve; the remaining 67 were pretreated with crizotinib (Xalkori). The median age was 55.0 years (range, 26-78), 100 patients were female (57.8%), and 127 (73.4%) had never smoked.

A total of 134 patients (77.5%) had an ECOG performance status of 1, and 162 (93.6%) had stage IV disease at enrollment. The most common disease histology was adenocarcinoma (94.8%), a majority of patients had 1 or 2 lines of prior therapy (51.4%), and most patients did not have prior anticancer chemotherapy (74.0%).

The primary end point was IRC-assessed cORR. Secondary end points included investigator-assessed ORR, PFS, disease control rate, duration of response (DOR), time to response, time to progression, and safety.

Additional efficacy results show that neither median DOR nor PFS was reached with the monotherapy treatment. Furthermore, the 24-month DOR rate was 78.6% (95% CI, 66.86%-86.56%), and the 24-month PFS rate was 70.5% (95% CI, 59.17%-79.16%).

Safety data reveal that the most common treatment-emergent adverse events (TEAEs) were increased aspartate aminotransferase (n = 132, 76.3%), diarrhea (n = 121, 69.9%), increased alanine aminotransferase (n = 117, 67.6%), vomiting (n = 92, 53.2%), and anemia (n = 85, 49.1%). Additionally, TEAEs leading to dose reduction were reported in 33 patients (19.1%), with TEAEs leading to discontinuation in 9 (5.2%). Additionally, 3 treatment-related AEs resulting in death were reported, including 2 patients naïve to TKIs due to hepatic failure and pneumonia, and 1 patient previously treated with crizotinib due to abnormal hepatic function.

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. January 2, 2025. Accessed January 3, 2025. https://tinyurl.com/335k27jz
2. Li W, Xiong A, Yang N, et al. Efficacy and safety of taletrectinib in Chinese patients with ROS1+ non–small cell lung cancer: the phase II TRUST-I study. J Clin Oncol. 2024;42(22):2660-2670. doi:10.1200/JCO.24.00731