FDA Approves Taletrectinib Label Update Showing 49.7-Month Median Duration of Response in ROS1+ NSCLC
核心洞察
The FDA approved a supplemental New Drug Application updating the taletrectinib label with a median duration of response of 49.7 months in TKI-naive advanced ROS1 (搜索)-positive NSCLC.
The update reflects a median follow-up of 51 months in the Phase 2 TRUST-I study and adds 14 months of data from the pivotal TRUST-I and TRUST-II trials.
TRUST-I reported an objective response rate of 90.3% and median progression-free survival of 49.6 months, with no changes to the label's safety sections.
The U.S. Food and Drug Administration has approved a supplemental New Drug Application for taletrectinib (Ibtrozi (搜索)), updating the label of the oral, CNS-active, selective ROS1 (搜索) inhibitor to include a median duration of response of 49.7 months in tyrosine kinase inhibitor (TKI)-naive patients with advanced ROS1-positive non-small cell lung cancer (搜索) (NSCLC). The approval was granted ahead of the previously scheduled January 4, 2027 FDA target action date.
The updated labeling incorporates additional follow-up from the pivotal Phase 2 TRUST-I and TRUST-II studies, reflecting a median follow-up of 51 months for patients in TRUST-I and an additional 14 months of data from both studies as of an August 2025 data cutoff, according to a news statement from Nuvation Bio, which announced the approval. The longer-term TRUST-I findings were published in the Journal of Clinical Oncology in 2026, and updated pooled results were presented at the AACR Annual Meeting 2026.
Durability of Response in TRUST-I
In the updated Phase 2 TRUST-I analysis (NCT04395677), 103 TKI-naive patients treated with taletrectinib 600 mg once daily had a median follow-up of 51 months. 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 duration of response reached 49.7 months and 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%.
In the pooled TRUST-I and TRUST-II dataset presented at AACR 2026, the TKI-naive population demonstrated a confirmed objective response rate of 89.8% and a median duration of response 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 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. The company stated that many patients remained on therapy for extended periods with a continued response, highlighting the long-term durability and tolerability of taletrectinib and reinforcing its role as a treatment option for patients with advanced ROS1 (搜索)-positive NSCLC.
The label update does not represent a new indication. Taletrectinib received full FDA approval on June 11, 2025, for adults with locally advanced or metastatic ROS1 (搜索)-positive NSCLC, including both TKI-naive and previously treated patients, based on data from the single-arm Phase 2 TRUST-I (NCT04395677) and TRUST-II (NCT04919811) studies.
Ongoing Development Program
The broader TRUST clinical development program also includes the Phase 3 TRUST-III study comparing taletrectinib with crizotinib in TKI-naive advanced ROS1 (搜索)-positive NSCLC, and the Phase 3 TRUST-IV study evaluating the therapy as adjuvant treatment following resection of early-stage ROS1-positive NSCLC.
ROS1 (搜索) 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.