Taletrectinib Under NMPA Review in China for First-Line ROS1+ NSCLC

The Center for Drug Evaluation of China’s National Medical Products Administration (NMPA) has accepted the second new drug application (NDA) for the next-generation ROS1 TKI taletrectinib (AB-106) in the first-line setting for patients with ROS1-positive non–small cell lung cancer (NSCLC) who have not been previously treated with ROS1 TKIs.¹

The application was supported by interim results from the phase 2 TRUST-I trial (NCT04395677), which were shared during the 2023 European Lung Cancer Congress. In the trial, taletrectinib demonstrated a confirmed objective response rate (cORR) of 92.5% (95% CI, 83.4%-97.5%) per independent review committee in evaluable patients who were TKI naive (n = 67).^1,2

Furthermore, the median time to response was 1.4 months (range, 1.2-4.2) in this patient population, and the median duration of response (DOR) was not yet reached (NR; range, 1.3-27.6). The disease control rate (DCR) for these patients was 95.5% (95% CI, 87.5%-99.1%), and the median progression-free survival was NR (range, 0.0-29.0).²

Notably, the first NDA for taletrectinib was submitted to the regulatory agency in November 2023 and was granted priority review based on data from the TRUST-I trial.¹

“Given the clinically demonstrated benefits of taletrectinib in the TRUST-I trial, we are pleased to see the second NDA accepted by the NMPA of China,” Hui Zhou, PhD, senior vice president of Innovent, stated in a press release.¹ “We will continue close communications with our partner AnHeart Therapeutics and regulatory authorities in China, hoping to bring this new generation of targeted therapy to all appropriate patients with ROS1-positive NSCLC as a standard initial treatment option.”

The oral, potent, brain-penetrant ROS1 inhibitor was also granted breakthrough therapy designation by the FDA in the United States for adult patients with advanced or metastatic ROS1-positive NSCLC who were ROS1 inhibitor–naive or who were previously treated with crizotinib (Xalkori); this designation was supported by preliminary findings from TRUST-I.^1,3

Patients were eligible to enroll in the multicenter, open-label, single-arm trial if they presented with locally advanced or metastatic NSCLC, were at least 18 years of age, had an ECOG performance status of 0 or 1, and showed evidence of a ROS1 fusion in tumor tissue. The study was made up of 2 stages. The first part was the lead-in stage, in which patients began treatment with taletrectinib. In the second part, patients were stratified by prior treatment status.²

Notably, the primary end point of the trial was IRC-assessed cORR, and secondary end points included, DOR, DCR, and ORR.²

“The acceptance of this NDA in China supports our belief in taletrectinib as a first-line treatment for [patients] with advanced or metastatic ROS1-positive NSCLC, and we are excited by the opportunity to bring a potentially transformative medicine to people earlier in their treatment journey,” Bing Yan, MD, president of AnHeart China, added in the news release. “We plan to work closely with our partner Innovent and regulatory authorities in China to continue progressing taletrectinib as part of our mission to improve the lives of [patients] with cancer.”

In addition to the research being done with taletrectinib in the TRUST-I trial, investigators are also conducting the global phase 2 TRUST-II trial (NCT04919811), which will further examine the safety and efficacy of single-agent taletrectinib in patients with advanced NSCLC.⁴

Notably, additional data from the TRUST-I trial are expected to be presented at an upcoming medical meeting in 2024.¹

“I am pleased this second NDA for taletrectinib has been accepted in China,” Professor Caicun Zhou, PhD, MD, director of the Department of Oncology, Shanghai Pulmonary Hospital in China; director of the Cancer Institute and chairman of the Oncology Department at Tongji University in China; and principal investigator of the TRUST-I trial, added in the news release. “We need additional options for our patients who are newly diagnosed with advanced or metastatic ROS1-positive NSCLC that may improve upon the first-generation medicines.”

References

1. Innovent and AnHeart Therapeutics announce the NMPA of China has accepted second NDA for taletrectinib for first-line treatment of ROS1-positive lung cancer. News release. Innovent Biologics. March 5, 2024. Accessed March 5, 2024. https://www.innoventbio.com/InvestorsAndMedia/PressReleaseDetail?key=434
2. Li W, Yang N, Li K, et al. Updated efficacy and safety of taletrectinib in patients with ROS1+ non–small cell lung cancer. Presented at: 2023 European Lung Cancer Congress; March 29-April 1, 2023; Copenhagen, Denmark. Abstract 14MO. https://www.anhearttherapeutics.com/file.cfm/14/docs/elcc_2023_talectrectinib.pdf
3. AnHeart Therapeutics receives FDA breakthrough therapy designation for taletrectinib in ROS1-positive non-small cell lung cancer. News release. AnHeart Therapeutics. August 3, 2022. Accessed March 5, 2024. https://www.anhearttherapeutics.com/news/press-releases/080322/
4. Taletrectinib phase 2 global study in ROS1 positive NSCLC (TRUST-II). ClinicalTrials.gov. Updated February 15, 2024. Accessed March 31, 2023. https://clinicaltrials.gov/ct2/show/NCT04919811