Taletrectinib Approved by FDA for ROS1+ Non-Small Cell Lung Cancer

Taletrectinib is approved for patients who have or have not received prior ROS1-targeted TKI.

The FDA has granted approval to the tyrosine kinase inhibitor (TKI) taletrectinib (Ibtrozi) for the treatment of patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer, according to an announcement from the agency.¹

The safety and efficacy of this therapy was assessed in the phase 1 TRUST-1 (NCT04395677) and phase 2 TRUST-II (NCT04919811) open-label, multi-center, single-arm trials. Patients enrolled may have had prior chemotherapy if their disease was advanced. The trials’ primary end points were confirmed overall response rate (ORR) and duration of response (DOR), as assessed by blinded independent central review.

TRUST-I enrolled 103 patients who had not received a prior ROS1-targeted TKI and 66 who had, while TRUST-II enrolled 54 patients who had not received prior ROS1-targeted TKI therapy and 47 who had.

Rate and Duration of Treatment Response

Treatment-naive patients in TRUST-I had an ORR of 90% (95% CI, 83%-95%), and those in TRUST-II had an ORR of 85% (95% CI, 73%-93%). DOR was 72% and 63%, respectively, for patients in those studies who had not received ROS1-targeted TKI treatment.

Moreover, in patients with prior TKI treatment, the ORR was 52% (95% CI, 39%-64%) for patients in TRUST-I and 62% (95% CI, 46%-75%) for those in TRUST-II. In those respective studies, 74% and 83% of participants had a DOR of at least 6 months.

TRUST-I, which takes place in Shanghai, China, is active but not recruiting, while TRUST-II, a global study, is still recruiting patients.^2,3

Key Safety Warnings

With regard to taletrectinib’s safety profile, its label includes warnings for hepatoxicity, interstitial lung disease and pneumonitis, QTc interval prolongation, hyperuricemia, myalgia with creatine phosphokinase elevation, skeletal fractures, and embryo-fetal toxicity.

According to a prior press release from the International Association for the Study of Lung Cancer, common adverse events (AEs) in TRUST-I and TRUST-II for patients who had not received a prior TKI were increased alanine aminotransferase (ALT), occurring in 66% of patients, increased aspartate aminotransferase (AST), occurring in 65% of patients, and diarrhea, occurring in 52% of patients. In the TKI pretreated cohorts, those AEs occurred in 66%, 65%, and 52% of patients, respectively.⁴

Taletrectinib was formerly known as AB-106 and DS-6051b.³

Reference

1. FDA approves taletrectinib for ROS1-positive non-small cell lung cancer. FDA. News release. June 11, 2025. Accessed June 11, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-taletrectinib-ros1-positive-non-small-cell-lung-cancer
2. A Study of AB-106 in Subjects With Advanced NSCLC Harboring ROS1 Fusion Gene. ClinicalTrials.gov. May 20, 2020. Updated October 30, 2023. Accessed June 11, 2025. https://clinicaltrials.gov/study/NCT04395677?id=NCT04395677&rank=1#contacts-and-locations
3. Taletrectinib Phase 2 Global Study in ROS1 Positive NSCLC (TRUST-II). ClinicalTrials.gov. June 9, 2021. Updated November 21, 2024. Accessed June 11, 2025. https://clinicaltrials.gov/study/NCT04919811?id=NCT04919811&rank=1#study-record-dates
4. Phase II Study of Taletrectinib Shows Durable Overall Response and Favorable Safety in Patients with ROS1+ Non-Small Cell Lung Cancer. International Association for the Study of Lung Cancer. News release. September 10, 2024. Accessed June 11, 2025. https://www.iaslc.org/iaslc-news/press-release/phase-ii-study-taletrectinib-shows-durable-overall-response-and-favorable