Taletrectinib Capsules (Ibtrozi)
August 15, 2025 4 minutes read
By William Elliott, MD, FACP, and James Chan, PharmD, PhD
The U.S. Food and Drug Administration (FDA) has approved a potent, selective, next-generation ROS Proto-Oncogene 1 (ROS1) receptor tyrosine kinase inhibitor (TKI), taletrectinib, for the treatment of ROS1-positive non-small cell lung cancer (NSCLC). Current FDA-approved ROS1 inhibitors include crizotinib, entrectinib, and repotrectinib. Taletrectinib was granted a priority review with breakthrough and orphan designations.1 It is distributed by Nuvation Bio, Inc as Ibtrozi.
Indications
Taletrectinib is indicated for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC.2
Dosage
The recommended dose is 600 mg (three capsules) orally once daily on an empty stomach (no food at least two hours before and two hours after taking the capsules). Treatment should be continued until disease progression or unacceptable toxicity.2 The dose should be modified based on the severity of adverse reactions.2 Taletrectinib is available as 200-mg capsules.
Potential Advantages
Taletrectinib has better central nervous system (CNS) penetration than repotrectinib, is more active against ROS1 secondary mutations than earlier TKIs, and is more selective against ROS1-resistant mutations, such as G2032R (a frequent secondary mutation), and ROS1 wild-type over tropomyosin receptor kinase B (TRKB).3 Inhibition of TBKB in the brain is one of the potential reasons for unwanted CNS-related adverse events associated with entrectinib.3
Potential Disadvantages
Taletrectinib is associated with several adverse reactions.2 These reactions include hepatotoxicity, interstitial lung disease/pneumonitis, QTc interval prolongation, hyperuricemia, myalgia with creatine phosphokinase elevation, skeletal fractures, and embryo-fetal toxicity.2 Adverse reactions (> 20%) include diarrhea; nausea; vomiting; constipation; dizziness; fatigue; a decrease in hemoglobin, lymphocytes, neutrophils, and albumin levels; as well as increases in triglycerides, cholesterol, potassium, and sodium levels. Taletrectinib is a substrate for CYP3A; therefore, concomitant use of strong/moderate CYP3A inhibitors and inducers should be avoided.
Comments
The efficacy of taletrectinib was evaluated in two multicenter single-arm, open-label clinical trials (TRUST-1 and TRUST-2) in participants with histologically confirmed, ROS1-positive, locally advanced or metastatic NSCLC.2,4 The major efficacy measures were confirmed overall response rate (ORR) and duration of response (DOR) according to RECIST v1.1 by a blinded independent central review. The efficacy population included 157 subjects who were naive to treatment with a ROS1 TKI and 113 who received one prior ROS1 TKI. Patient median age was 56 years, 66.7% never smoked, 93.8% had stage IV disease at enrollment, and 57.1% were female. Tumor assessment with imaging was performed every six weeks for the first 24 weeks, every nine weeks for the following year, and every 12 weeks thereafter. The overall response in the two studies was 88.8%, with 84% partial responses in TKI-naive subjects. Median DOR was 44.2 months.4 In the ROS1 TKI-treated population, the confirmed ORR was 55.8% with a median DOR of 16.6 months. Fifty-one percent had a partial response, and 32% had stable disease. Eight of 15 participants had a baseline G2032R mutation and responded.4
Clinical Implications
ROS1 NSCLC is a rare cancer with a prevalence of 0.9% to 2.6% and tends to occur in females, never-smokers, and it tends to be diagnosed at an advanced stage, with approximately one-third of patients having brain metastasis.4 This is a result of the ROS1 gene fusing with part of another gene (i.e., rearrangement). Currently, there are three ROS1 TKI-approved drugs, crizotinib, entrectinib, and repotrectinib. These have some limitations — crizotinib is not active against G2032R, and both entrectinib and repotrectinib carry a warning for CNS adverse events, including dizziness, ataxia, and cognitive impairment.5,6 In addition, entrectinib has a warning for the risk of congestive heart failure. Taletrectinib showed higher CNS penetration and, therefore, may be an attractive option for ROS1 NSCLC with secondary mutations and brain metastasis. The cost for a 30-day supply is $29,488.
William T. Elliott, MD, FACP, is Assistant Clinical Professor of Medicine, University of California, San Francisco.
James Chan, PharmD, PhD, is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
References
- U.S. Food and Drug Administration. FDA approves taletrectinib for ROS1-positive non-small cell lung cancer. Published June 11, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-taletrectinib-ros1-positive-non-small-cell-lung-cancer
- U.S. Food and Drug Administration. Ibtrozi prescribing information. Nuvation Bio, Inc. Revised June 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219713s000lbl.pdf
- Nagasaki M, Brazel D, Ou S-HI. Taletrectinib for the treatment of ROS-1 positive non-small cell lung cancer: A drug evaluation of phase I and II data. Expert Opin Investig Drugs 2024;33(2):79-84.
- Pérol M, Pennell NA, Liu G, et al. Taletrectinib in ROS1+ non-small cell lung cancer: TRUST. J Clin Oncol 2025;43(16):1920-1929.
- U.S. Food and Drug Administration. Augtyro prescribing information. E.R. Squibb & Sons, LLC. Revised June 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/218213s001lbl.pdf
- U.S. Food and Drug Administration. Rozlytrek prescribing information. Genetech, Inc. Revised October 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/212725Orig1s009lbl.pdf
The U.S. Food and Drug Administration has approved a potent, selective, next-generation ROS Proto-Oncogene 1 (ROS1) receptor tyrosine kinase inhibitor, taletrectinib, for the treatment of ROS1-positive non-small cell lung cancer.
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