Taletrectinib Wins Japanese Approval for ROS1+ Advanced NSCLC

Taletrectinib (Ibtrozi) has been approved by Japan’s Ministry of Health, Labour and Welfare (MHLW) for the treatment of adult patients with ROS1-positive unresectable, advanced and/or recurrent non–small cell lung cancer (NSCLC).1

The regulatory decision was supported by data from the phase 2 TRUST-I (NCT04395677) and TRUST-II (NCT04919811) trials. Findings from a pooled analysis of the 2 studies showed that TKI-naive patients (n = 160) achieved a confirmed overall response rate (ORR) of 88.8% (95% CI, 82.8%-93.2%) and a disease control rate (DCR) of 95.0% (95% CI, 90.4%-97.8%).2 Patients previously treated with a ROS1 TKI (n = 113) experienced a confirmed ORR and DCR of 55.8% (95% CI, 46.1%-65.1%) and 87.6% (95% CI, 80.1%-93.1%), respectively.

The intracranial ORR (IC-ORR) was 76.5% (95% CI, 50.1%-93.2%) and 65.6% (95% CI, 46.8%-81.4%) in the TKI-naive and TKI-pretreated populations, respectively.

Data from TRUST-I and TRUST-II also supported the June 2025 FDA approval of taletrectinib for the treatment of patients with locally advanced or metastatic, ROS1-positive NSCLC.3

“Building on the regulatory approvals for [taletrectinib] in the United States and China, this additional approval by the MHLW further underscores the best-in-class potential and promise that [taletrectinib] holds for patients living with advanced ROS1-positive NSCLC around the globe," David Hung, MD, founder, president, and chief executive officer of Nuvation Bio, stated in a news release.1 “We remain steadfastly committed to bringing forward innovative cancer treatments that can help patients stay ahead of their disease.”

How Was the TRUST Clinical Trial Program Designed?

TRUST-I was an open-label, single-arm, nonrandomized study conducted in China that evaluated taletrectinib in patients with locally advanced or metastatic, ROS1-positive NSCLC.1,2 Patients naive to a ROS1 TKI were treated in cohort 1, and those who progressed on prior treatment with crizotinib (Xalkori) were enrolled in cohort 2.2

In the global, multicenter, open-label, single-arm, nonrandomized TRUST-II study, taletrectinib was evaluated in patients with ROS1-positive advanced NSCLC who were naive to a TKI or previously treated with crizotinib or entrectinib (Rozlytrek).

All patients in both trials were allowed to have received up to 1 prior line of chemotherapy. Patients also needed to have at least 1 measurable lesion per RECIST 1.1 criteria; locally documented evidence of a ROS1 gene fusion; an ECOG performance status of 0 or 1; adequate hepatic, renal, and bone marrow function; and a QT interval within 470 ms. Patients with brain metastases were allowed to enroll if they were asymptomatic or previously treated and stable.

Patients in both trials received taletrectinib at 600 mg once per day in 21-day treatment cycles, with treatment continuing until disease progression or unacceptable toxicity.

Confirmed ORR per independent review committee assessment served as the primary end point in both studies. Key secondary end points comprised DCR, duration of response, time to response, and progression-free survival. IC-ORR and IC-DCR were also evaluated in patients with brain metastases.

What Adverse Effects Are Associated With Taletrectinib?

Among evaluable patients in the 2 studies treated with taletrectinib at 600 mg once per day (n = 352), the most common treatment-emergent adverse effects (TEAEs) of any grade included increased aspartate aminotransferase levels (72%), increased alanine aminotransferase levels (68%), diarrhea (64%), nausea (46%), and vomiting (44%); most liver enzyme elevations were grade 1 or 2, and the majority of gastrointestinal-related toxicities were grade 1. Neurologic TEAEs reported in at least 10% of patients included dizziness (21%), dysgeusia (15%), and headache (11%), with most occurring at grade 1.

TEAEs led to treatment discontinuation in 7% of patients, including 3% who discontinued due to treatment-related TEAEs. TEAEs leading to discontinuation that occurred in more than 1 patient included pneumonia (n = 3), interstitial lung disease (n = 2), and abnormal hepatic function (n = 2).

References

1. Nuvation Bio receives approval from Japan’s Ministry of Health, Labour and Welfare for Ibtrozi for patients with advanced ROS1-positive non-small cell lung cancer. News release. Nuvation Bio. https://investors.nuvationbio.com/news/news-details/2025/Nuvation-Bio-Receives-Approval-from-Japans-Ministry-of-Health-Labour-and-Welfare-for-IBTROZITM-for-Patients-with-Advanced-ROS1-positive-Non-Small-Cell-Lung-Cancer/default.aspx
2. Pérol M, Li W, Pennell NA, et al. Taletrectinib in ROS1+ non-small cell lung cancer: TRUST. J Clin Oncol. 2025;43(16):1920-1929. doi:10.1200/JCO-25-00275
3. FDA approves taletrectinib for ROS1-positive non-small cell lung cancer. FDA. June 11, 2025. Accessed September 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-taletrectinib-ros1-positive-non-small-cell-lung-cancer