Reference Detail

Ref Type

Journal Article

PMID

(38822758)

Authors

Li W, Xiong A, Yang N, Fan H, Yu Q, Zhao Y, Wang Y, Meng X, Wu J, Wang Z, Liu Y, Wang X, Qin X, Lu K, Zhuang W, Ren Y, Zhang X, Yan B, Lovly CM, Zhou C

Title

Efficacy and Safety of Taletrectinib in Chinese Patients With ROS1+ Non-Small Cell Lung Cancer: The Phase II TRUST-I Study.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of clinical oncology : official journal of the American Society of Clinical Oncology			2024 Jun 01	JCO2400731	J Clin Oncol

URL

Abstract Text

Taletrectinib, a highly potent, CNS-active, ROS1 tyrosine kinase inhibitor (TKI), has demonstrated high and durable response rates, high intracranial objective response rate (ORR), prolonged progression-free survival (PFS), and activity against G2032R with a favorable safety profile. We report outcomes from the pivotal TRUST-I study (ClinicalTrials.gov identifier: NCT04395677) of taletrectinib for ROS1+ non-small cell lung cancer in China.TRUST-I evaluated TKI-naїve and crizotinib-pretreated patients. The primary end point was confirmed ORR (cORR) by independent review committee; key secondary end points included duration of response (DOR), PFS, and safety.As of November 2023, 173 patients were enrolled (median age, 55 years; 58% female; 73% never smoked; TKI naїve: n = 106; crizotinib pretreated: n = 67). In TKI-naїve patients, cORR and intracranial cORR were 91% and 88%, respectively, and 52% and 73% in crizotinib-pretreated patients. In TKI-naїve patients, median DOR and median PFS were not reached (NR) with 22.1-month and 23.5-month follow-up, respectively. In crizotinib-pretreated patients, the median DOR was 10.6 months (95% CI, 6.3 months to NR; 8.4-month follow-up), and the median PFS was 7.6 months (95% CI, 5.5 to 12.0 months; 9.7-month follow-up). Eight of 12 patients (67%) with G2032R mutations responded. The most frequent treatment-emergent adverse events (TEAEs) were increased AST (76%), diarrhea (70%), and increased ALT (68%), most of which were grade 1-2. Incidences of neurologic TEAEs were low (dizziness: 23%; dysgeusia: 10%) and mostly grade 1. Discontinuations (5%) and dose reductions (19%) due to TEAEs were low.Taletrectinib continues to show high and durable overall responses, prolonged PFS, robust activity against intracranial lesions and acquired resistance mutations including G2032R, and a favorable safety profile with a low incidence of neurologic TEAEs.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
ROS1 fusion ROS1 G2032R	lung non-small cell carcinoma	predicted - sensitive	Taletrectinib	Case Reports/Case Series	Actionable	In a Phase II trial (TRUST-I), Taletrectinib (DS6051b) treatment resulted in an objective response rate of 66.7% (8/12, all partial responses) in patients with non-small cell lung cancer harboring ROS1 fusions with secondary ROS1 G2032R mutations (PMID: 38822758; NCT04395677).	38822758
ROS1 fusion	lung non-small cell carcinoma	predicted - sensitive	Taletrectinib	Phase II	Actionable	In a Phase II trial (TRUST-I), Taletrectinib (DS6051b) treatment in non-small cell lung cancer patients with ROS1 fusions resulted in a 90.6% (96/106) overall response rate (ORR) and 95.3% disease control rate (DCR) in TKI-naive patients and 51.5% (34/66) ORR and 83.3% DCR in crizotinib-pretreated patients, intracranial ORR of 87.5% (7/8) and DCR of 100% in patients with baseline brain lesions, and partial responses in 8 of 12 patients with secondary ROS1 G2032R mutations (PMID: 38822758; NCT04395677).	38822758