November 22, 2023

Courtney Flaherty

The Center for Drug Evaluation of China’s National Medical Products Administration has accepted the new drug application seeking the approval of the next-generation ROS1 TKI taletrectinib for the treatment of patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer with prior exposure to a ROS1 TKI.

Caicun Zhou, MD, PhD

Caicun Zhou, MD, PhD

The Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has accepted the new drug application (NDA) seeking the approval of the next-generation ROS1 TKI taletrectinib (AB-106) for the treatment of patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) with prior exposure to a ROS1 TKI.1

The application was supported by interim results from the phase 2 TRUST-I trial (NCT04395677), in which taletrectinib elicited a confirmed overall response rate (cORR) of 92.5% (95% CI, 83.4%-97.5%) per independent review committee (IRC) assessment in evaluable patients who were not previously exposed to a TKI (n = 67).2 Evaluable patients who were previously exposed to a TKI (n = 38) achieved an IRC-assessed cORR of 52.6% (95% CI, 35.8%-69.0%) with the agent.

Moreover, in 12 patients with measurable brain metastases, the intracranial ORR (IC-ORR) was 91.7% (95% CI, 61.5%-99.8%), and all patients achieved intracranial disease control (95% CI, 73.5%-100.0%). These robust responses were observed regardless of the number of prior lines of therapy.

Regarding safety, taletrectinib was tolerable in both patient populations, and was associated with a low incidence of neurological adverse effects (AEs). Treatment-emergent AEs (TEAEs) were mostly low grade, and treatment discontinuations and dose reductions because of TEAEs were infrequent.

“We have extremely limited options for our patients with ROS1-positive NSCLC, especially those with brain metastases who represent more than one-third of patients, and those who go on to develop resistant mutations, which is more than half of patients. Once patients progress on the current options, there are no approved treatments,” Caicun Zhou, MD, PhD, a principal investigator and oncologist at Shanghai Pulmonary Hospital in China, stated in a news release.1 “I hope this NDA represents a step toward making another option available to the ROS1-positive NSCLC patient community in China.”

TRUST-I is a multicenter, open-label, single-arm trial enrolling 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.2

In the lead-in phase of the study, patients received either 400 mg or 600 mg of taletrectinib per day. Stage 2 of the study enrolled patients who were TKI naive or TKI exposed onto 2 separate cohorts. Patients in both cohorts received 600 mg of taletrectinib per day.

The trial’s primary end point was IRC-assessed cORR per RECIST v1.1 criteria. Key secondary end points included duration of response, disease control rate, IC-ORR, progression-free survival, time to response, and overall survival.

Taletrectinib was previously granted breakthrough therapy designationby the FDA in August 2022 for use in adult patients with advanced or metastatic ROS1-positive NSCLC who were ROS1 inhibitor naive or who had previously received crizotinib (Xalkori).3

That same year, the agent was also granted breakthrough therapy designation by the CDE in China for both ROS1 TKI–exposed and –naive patients with advanced or metastatic ROS1-positive NSCLC. Both regulatory decisions were based on preliminary data from TRUST-I.1,3

“We are encouraged by the best-in-class efficacy and safety profile that taletrectinib demonstrated in the TRUST-I trial, and are excited about the NDA acceptance in China,” Dr Hui Zhou, senior vice president of Innovent, stated in the news release.1 “Together with our partner AnHeart [Therapeutics], we will work closely with the NMPA to bring this precision therapy to NSCLC patients.”

In addition to its ongoing evaluation in the TRUST-I trial in China, taletrectinib is currently being evaluated in the global phase 2 TRUST-II trial (NCT04919811), which aims to validate the data from TRUST-I in a global population. Interim data from TRUST-II were reported at the 2023 ESMO Congress. In TRUST-II, taletrectinib produced a cORR of 92.0% (95% CI, 74.0%-99.0%) in evaluable TKI-naive patients (n = 25) and a cORR of 57.1% (95% CI, 34.0%-78.2%) in patients who were TKI exposed (n = 21).4

“Acceptance of our China NDA marks an important milestone for AnHeart and is the first regulatory submission for taletrectinib globally. We would like to thank all the doctors and patients who participated in the clinical trials that support this submission,” said Bing Yan, MD, chief medical officer of AnHeart, in the news release.1 “We look forward to working with our partner Innovent and the regulatory authorities in China to hopefully make taletrectinib available to patients in need as soon as possible.”

References

  1. AnHeart Therapeutics and Innovent announce China’s NMPA has accepted a new drug application for taletrectinib (ROS1 inhibitor). News release. AnHeart Therapeutics. November 22, 2023. Accessed November 22, 2023. https://www.anhearttherapeutics.com/news/press-releases/112223/

  2. Li W, Yang N, Li K, et al. Updated efficacy and safety of taletrectinib in patients with ROS1+ non–small cell lung cancer. J. Thor Onc. 2023;18(4):S47-S48. doi:10.1016/S1556-0864(23)00268-X

  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 November 22, 2023. https://www.anhearttherapeutics.com/news/press-releases/080322/

  4. Efficacy and safety of taletrectinib in patients (Pts) with ROS1+ non-small cell lung cancer (NSCLC): Interim analysis of global TRUST-II study. Ann Oncol. 2023; 34(2): S755-S85. doi:0.1016/annonc/annonc1331