Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jan;19(2):123-135.
doi: 10.2217/fon-2022-1059. Epub 2023 Mar 6.

TRUST-II: a global phase II study of taletrectinib in ROS1-positive non-small-cell lung cancer and other solid tumors

Misako Nagasaka  1   2 , Yuichiro Ohe  3 , Caicun Zhou  4 , Chang-Min Choi  5 , Nong Yang  6 , Geoffrey Liu  7 , Enriqueta Felip  8 , Maurice Pérol  9 , Benjamin Besse  10 , Jorge Nieva  11 , Luis Raez  12 , Nathan A Pennell  13 , Anastasios Dimou  14 , Filippo de Marinis  15 , Fortunato Ciardiello  16 , Takashi Seto  17 , Zheyi Hu  18 , Max Pan  18 , Weiqing Wang  18 , Shuanglian Li  18 , Sai-Hong I Ou  1   2
Affiliations
Free article

TRUST-II: a global phase II study of taletrectinib in ROS1-positive non-small-cell lung cancer and other solid tumors

Misako Nagasaka et al. Future Oncol. 2023 Jan.
Free article

Abstract

Crizotinib and entrectinib have been approved to treat ROS1 fusion-positive (ROS1+) non-small-cell lung cancer. However, unmet needs remain, including treatment of patients with resistance mutations, efficacy in brain metastasis and avoidance of neurological side effects. Taletrectinib was designed to: improve efficacy; overcome resistance to first-generation ROS1 inhibitors; and address brain metastasis while conferring fewer neurological adverse events. All of these features are demonstrated and supported by the interim data from the regional phase II TRUST-I clinical study. Here we describe the rationale and design of TRUST-II, a global phase II study of taletrectinib in patients with locally advanced/metastatic ROS1+ non-small-cell lung cancer and other ROS1+ solid tumors. The primary end point is confirmed objective response rate. Secondary end points include duration of response, progression-free survival, overall survival and safety. This trial is enrolling patients in North America, Europe and Asia.

Trial registration: ClinicalTrials.gov NCT04919811.

Keywords: ROS1 kinase fusion; ROS1G2032R; TRKB; brain metastasis; brain penetration; intracranial antitumor activity; neoplasm drug resistance; non-small-cell lung cancer; taletrectinib; tyrosine kinase inhibitors.

Plain language summary

The targeted therapies crizotinib and entrectinib are the first options available to treat a type of lung cancer called ROS1 fusion-positive non-small-cell lung cancer (ROS1+ NSCLC). However, not all patients with ROS1+ NSCLC respond to these drugs. In addition, most patients who take these drugs find their cancer eventually develops resistance and begins to grow again. Patients with disease that has spread (metastasized) to the brain have worse outcomes. Taletrectinib is a new type of targeted therapy that is being developed to treat people who have metastatic ROS1+ NSCLC. Data from a regional phase II clinical trial showed that taletrectinib is well tolerated, effective for patients who have never taken a ROS1 targeted therapy and inhibits ROS1+ NSCLC for patients whose cancer has developed some types of resistance to these drugs. It has also been shown to treat ROS1+ NSCLC tumors that have spread to the brain. This article discusses the rationale and design of a new trial called TRUST-II, which is a global phase II clinical trial looking at how well taletrectinib works and how safe it is. TRUST-II is actively enrolling patients in North America, Europe and Asia. Clinical Trial Registration: NCT04919811 (ClinicalTrials.gov).

PubMed Disclaimer

Publication types

MeSH terms

Associated data

LinkOut - more resources