FDA Approves Taletrectinib Label Update With 49.7-Month Duration of Response in ROS1+ NSCLC

The U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for taletrectinib (IBTROZI), updating the drug’s label with longer-term duration-of-response data in patients with tyrosine kinase inhibitor (TKI)-naïve, advanced ROS1-positive non-small cell lung cancer (NSCLC).

The updated label now includes a median duration of response (DOR) of 49.7 months among TKI-naïve patients enrolled in the Phase 2 TRUST-I study, based on a median follow-up of 51 months. The approval incorporates additional follow-up from the pivotal TRUST-I and TRUST-II studies and was granted ahead of the previously scheduled January 4, 2027 FDA target action date.

Importantly, the update does not represent a new indication for taletrectinib. The therapy was originally granted full FDA approval in June 2025 for adults with locally advanced or metastatic ROS1-positive NSCLC, including both TKI-naïve and previously treated patients.

Longer-Term Data From TRUST-I

In the updated Phase 2 TRUST-I trial (NCT04395677) analysis, 103 TKI-naïve patients treated with taletrectinib 600 mg once daily had a median follow-up of 51 months.

The independent review committee-assessed objective response rate was 90.3%, including complete responses in 4.9% and partial responses in 85.4% of patients. Median DOR reached 49.7 months, while median progression-free survival was 49.6 months. Median overall survival had not been reached, and the estimated 3-year overall survival rate was 65.3%.

The longer-term TRUST-I findings were published in the Journal of Clinical Oncology in 2026. Updated pooled results from TRUST-I and TRUST-II were also presented at the AACR Annual Meeting 2026, where the TKI-naïve population demonstrated a confirmed objective response rate of 89.8% and median DOR of 49.7 months.

Nuvation Bio said the longer follow-up provides additional evidence regarding the durability of response to taletrectinib when used earlier in the treatment course.

David Hung, MD, Founder, President and CEO of Nuvation Bio, described the updated data as providing physicians and patients with “a clearer sense of how long they might expect to stay on treatment.”

Safety Profile Remains Unchanged

According to Nuvation Bio, the FDA-approved update resulted in no changes to the safety sections of the taletrectinib label, and no new safety signals were identified with longer follow-up.

Taletrectinib is an oral, CNS-active, selective ROS1 inhibitor developed for ROS1-positive NSCLC. The FDA initially approved the therapy on June 11, 2025, based on data from the single-arm Phase 2 TRUST-I (NCT04395677) and TRUST-II (NCT04919811) studies.

The broader TRUST clinical development program also includes the Phase 3 TRUST-III study comparing taletrectinib with crizotinib in TKI-naïve advanced ROS1-positive NSCLC and the Phase 3 TRUST-IV study evaluating the therapy as adjuvant treatment following resection of early-stage ROS1-positive NSCLC.

ROS1 alterations are estimated to occur in approximately 2% of NSCLC cases. Because patients with ROS1-positive disease can develop central nervous system metastases, CNS activity remains an important consideration in the development and selection of targeted therapies for this population.

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