FDA Approves Taletrectinib Label Update Reflecting Durable Responses in TKI-Naïve ROS1-Positive Non-Small Cell Lung Cancer

Clinical Summary:

• Regulatory Update: The FDA approved a supplemental new drug application for taletrectinib that updates the prescribing information with longer-term duration-of-response data from the TRUST-I study in TKI-naïve patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer.
• Key Outcomes: With extended follow-up, median duration of response reached 49.7 months among TKI-naïve patients in TRUST-I. The update incorporates additional follow-up from the pivotal TRUST-I and TRUST-II studies, with no new safety signals or changes to the safety sections of the prescribing information.
• Clinical Relevance: The updated label provides more mature evidence of sustained response durability with taletrectinib in TKI-naïve ROS1-positive advanced NSCLC, strengthening the clinical evidence supporting early use of this ROS1-directed therapy.

The US Food and Drug Administration (FDA) has approved a supplemental new drug application (sNDA) for taletrectinib (Ibtrozi; Nuvation Bio), updating the prescribing information with longer-term duration of response data in tyrosine kinase inhibitor (TKI)-naïve patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).

Taletrectinib previously received full FDA approval in June 2025 for adults with locally advanced or metastatic ROS1-positive NSCLC across lines of therapy. The supplemental approval does not change the indication but incorporates more mature efficacy data from the pivotal TRUST-I and TRUST-II studies.

The updated label reflects a median follow-up of 51 months among patients enrolled in TRUST-I and incorporates an additional 14 months of follow-up from TRUST-I and TRUST-II through an August 2025 data cutoff.

Among TKI-naïve patients in TRUST-I, median duration of response reached 49.7 months, representing more than 4 years of sustained response. According to the company, multiple patients remained on therapy with ongoing responses for several years.

TRUST-I and TRUST-II are phase 2, single-arm trials evaluating taletrectinib in adults with advanced ROS1-positive NSCLC. TRUST-I enrolled 173 patients in China, while the global TRUST-II study enrolled 189 patients. The primary end point of both studies was confirmed objective response rate assessed by independent review committee.

The longer-term follow-up did not result in changes to the safety sections of the prescribing information, and no new safety signals were identified.

Taletrectinib is an oral, CNS-active, selective ROS1 inhibitor. Warnings and precautions include hepatotoxicity, interstitial lung disease (ILD)/pneumonitis, QTc interval prolongation, hyperuricemia, myalgia with creatine phosphokinase elevation, skeletal fractures, and embryo-fetal toxicity.

Hepatotoxicity remains an important safety consideration. Increased aspartate aminotransferase occurred in 88% of patients, including grade 3/4 events in 10%, while increased alanine aminotransferase occurred in 85%, including grade 3/4 events in 13%. Fatal hepatic events occurred in 0.6% of patients.

ILD/pneumonitis occurred in 2.3% of patients, including grade 3/4 events in 1.1%. One fatal ILD event was reported at the 400-mg daily dose.

QTc interval prolongation was also observed. Among patients with postbaseline electrocardiographic assessment, a QTcF increase of more than 60 milliseconds from baseline occurred in 13%, while QTcF greater than 500 milliseconds occurred in 2.6%. Grade 3 or higher QTc prolongation occurred in 3.4%.

The most frequently reported adverse reactions included diarrhea, nausea, vomiting, dizziness, rash, constipation, and fatigue. The most common grade 3/4 laboratory abnormalities included increased alanine aminotransferase, increased aspartate aminotransferase, decreased neutrophils, and increased creatine phosphokinase.

The label update provides clinicians with longer-term evidence of response durability in TKI-naïve ROS1-positive disease without identifying new safety concerns during extended follow-up.

Source:

Nuvation Bio. Nuvation Bio announces FDA approval of supplemental new drug application for IBTROZI® (taletrectinib) with updated duration of response in TKI-naïve advanced ROS1-positive non-small cell lung cancer. Accessed on: September 17, 2026. https://investors.nuvationbio.com/news/news-details/2026/Nuvation-Bio-Announces-FDA-Approval-of-Supplemental-New-Drug-Application-for-IBTROZI-taletrectinib-with-Updated-Duration-of-Response-in-TKI-Nave-Advanced-ROS1-Positive-Non-Small-Cell-Lung-Cancer/default.aspx