FDA Grants Breakthrough Therapy Designation to Taletrectinib for ROS1+ Non–Small Cell Lung Cancer


Supported by data from an ongoing phase 2 trial, the ROS1 inhibitor taletrectinib was granted breakthrough therapy designation for the treatment of certain patients with advanced or metastatic ROS1-positive non–small cell lung cancer.

The FDA granted breakthrough therapy designation to the ROS1 inhibitor taletrectinib for the treatment of patients with advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC) who are naïve to treatment with ROS1 tyrosine kinase inhibitors (TKI) or who were previously treated with crizotinib (Xalkori), according to a press release from the drug’s developer, AnHeart Therapeutics.1

Data supporting the designation include results from the ongoing phase 2 TRUST trial (NCT04395677) examining taletrectinib in Chinese patients with advanced NSCLC whose tumors harbor ROS1 gene fusions, for which preliminary data were presented at the 2022 American Society of Clinical Oncology Annual Meeting.2

“There is a high unmet need for this specific patient population in lung cancer, where very few treatment options are available,” Lian Li, MD, PhD, chief medical officer (US) of AnHeart, said in a press release. “In the TRUST Phase 2 trial, taletrectinib showed promising antitumor activity against ROS1-fusion and resistant mutations in adult patients with ROS1-positive NSCLC, with a favorable safety profile.”

In 67 patients with ROS1 fusion–positive, TKI naïve NSCLC, the confirmed objective response rate was 92.5% with a disease control rate of 95.5%. In those who were previously treated with crizotinib (n = 38), corresponding rates were 50.0% and 78.9%. Among 12 patients with brain metastases and measurable brain lesions at baseline, intracranial confirmed objective response occurred in 91.7% of patients with all achieving intracranial disease control.

Regarding safety, taletrectinib was generally well tolerated with most treatment-emergent adverse events (TRAEs) being grade 1 or 2 in severity. The most common TRAEs were low-grade diarrhea and transient alanine/aspartate aminotransferase. Neurological AEs were infrequently reported.

Other common AEs associated with other ROS1 inhibitors—such as edema, headache, dizziness, and musculoskeletal disorders occurred less frequently with taletrectinib. This is attributable to the agent’s selective inhibition of the ROS1 kinase over TRKB which reduces central nervous system AEs associated with TRKB inhibition.

The primary end point of the TRUST trial is best overall response by independent review committee, with secondary end points of safety, duration of response, time to response, progression-free survival, and intracranial response. Patients were eligible if they had histologically or cytologically confirmed locally advanced NSCLC with positivity for ROS1 fusions as determined by fluorescence in situ hybridization or real-time polymerase chain reaction or next-generation sequencing assays. Patients could either be naïve to treatment with a TKI or have disease progression following crizotinib.

Ongoing research continues in the global phase 2 TRUST-II trial (NCT04919811) that is actively enrolling patients across sites in North America, Europe, and Asia.

“Taletrectinib also showed better brain penetration and intracranial antitumor activity in comparison to other ROS1 inhibitors. Patients with ROS1-positive NSCLC desperately need new therapeutic options, and we look forward to our ongoing dialogue with the FDA to accelerate the development of taletrectinib for patients in the US,” concluded Li.


  1. 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 August 4, 2022. https://bwnews.pr/3oZrw2o
  2. AnHeart Therapeutics and Innovent Biologics present updated phase 2 efficacy and safety data of taletrectinib (ROS1 inhibitor) at ASCO 2022. News release. AnHeart Therapeutics. June 6, 2022. Accessed August 4, 2022. https://bwnews.pr/3Skkkvv
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