FDA

Ibtrozi OK'd for advanced ROS1-positive NSCLC

June 16, 2025

Brand name: Ibtrozi

Generic name: taletrectinib

Manufacturer: Nuvation Bio

Approval date: June 9, 2025

FDA approved Ibtrozi (taletrectinib) for the treatment of adult patients with locally advanced or metastatic ROS1-positive (ROS1+) non-small cell lung cancer (NSCLC).

Efficacy

Approval was supported by data from 2 single-arm, open-label trials, TRUST-I (NCT04395677) and TRUST-II (NCT04919811) that evaluated taletrectinib in 270 patients with histologically confirmed, ROS1-positive, locally advanced or metastatic NSCLC. In both trials, study participants received taletrectinib 600 mg orally once daily. Primary endpoint was overall response rate (ORR).

Ibtrozi achieved a confirmed overall response rate (cORR) of 90% in TKI-naïve patients in TRUST-I and 85% in TRUST-II. The median duration of response (DOR) was not yet reached for either trial, based on a cutoff date that is nearly five months later than that of the pooled TRUST-I and TRUST-II analysis published in April. For TRUST-I, with a median follow-up for responses of 40 months, the longest DOR was observed at 46.9 months and ongoing. For TRUST-II, with a median follow-up for responses of 19 months, the longest DOR was observed at 30.4 months and ongoing as of October 2024. Given the single-arm nature of the TRUST clinical studies, median progression-free survival (PFS) is not provided.

Consistent results were also observed among patients who were previously treated with a ROS1 TKI (TKI-pretreated). In TRUST-I, treatment with Ibtrozi achieved a cORR of 52% and median DOR of 13.2 months for TKI-pretreated patients, with median follow-up for responses of 33 months. In TRUST-II, treatment with Ibtrozi achieved a cORR of 62%, and as of October 2024 the median DOR was 19.4 months in these patients, with a median follow-up for responses of 19 months.

Ibtrozi was designed to penetrate the CNS and has demonstrated consistent intracranial responses in patients with measurable brain mets at baseline. An intracranial response was achieved in 73% of TKI-naive patients (11/15) and 63% of TKI-pretreated patients (15/24).

Safety

The most frequently reported adverse reactions (≥20%) were: diarrhea, nausea, vomiting, dizziness, rash, constipation, and fatigue. The most frequently reported grade 3 or 4 lab abnormalities (≥5%) were: increased ALT and AST, decreased neutrophils, and increased CPK.

Recommended dose

The recommended dosage of Ibtrozi is 600 mg PO once daily on an empty stomach. Treatment should be continued until disease progression or unacceptable toxicity.

Sources:

Ibtrozi (taletrectinib) [package insert]. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219713s000lbl.pdf Revised June 2025. Accessed June 13, 2025.

US Food and Drug Administration approves Nuvation Bio’s Ibtrozi™ (taletrectinib), a next-generation oral treatment for advanced ROS1-positive non-small cell lung cancer. [News release]. 2025. https://investors.nuvationbio.com/news/news-details/2025/U-S--Food-and-Drug-Administration-Approves-Nuvation-Bios-IBTROZI-taletrectinib-a-Next-Generation-Oral-Treatment-for-Advanced-ROS1-Positive-Non-Small-Cell-Lung-Cancer/default.aspx