Efficacy and Safety of Taletrectinib in Chinese Patients With ROS1+ Non–Small Cell Lung Cancer: The Phase II TRUST-I Study
Open accessAbstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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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The recommended phase II dose of taletrectinib is 600 mg once daily.
“The recommended phase II dose (600 mg once daily) was established in two phase I trials conducted in the United States and Japan21,22 and confirmed during the safety lead-in of TRUST-I.20”
From Taletrectinib in <i>ROS1</i> + Non–Small Cell Lung Cancer: TRUST (2025) · cites this paper as [20]
The integrated analysis is feasible because both studies had similar pivotal study designs, inclusion and exclusion criteria, primary and secondary end points, identical efficacy and safety assessment methods and schedules, and consistent statistical approaches.
“This integrated analysis is feasible because both studies had similar pivotal study designs, inclusion and exclusion criteria, and primary and secondary end points. In addition, the efficacy and safety assessment methods and their schedules were identical, and statistical approaches were consistent between these studies.19,20”
From Taletrectinib in <i>ROS1</i> + Non–Small Cell Lung Cancer: TRUST (2025) · cites this paper as [20]
Efficacy and safety results with taletrectinib observed in TRUST-I are generalizable to a global population of patients with ROS1+ NSCLC.
“In this integrated analysis, we show that the efficacy and safety results with taletrectinib observed in TRUST-I20 are generalizable to a global population of patients with ROS1+ NSCLC.”
From Taletrectinib in <i>ROS1</i> + Non–Small Cell Lung Cancer: TRUST (2025) · cites this paper as [20]
Taletrectinib is an oral, CNS-active, next-generation ROS1 TKI with 11- to 20-fold selectivity over TrKB.
“Taletrectinib is an oral, CNS-active, next-generation ROS1 TKI with 11- to 20-fold selectivity over TrKB, which may translate into lower rates of, less severe, or limited spectrum of neurologic AEs.19,20”
From Taletrectinib in <i>ROS1</i> + Non–Small Cell Lung Cancer: TRUST (2025) · cites this paper as [20]
The selectivity of taletrectinib for ROS1 over TrKB may explain the lower rates and narrower spectrum of neurologic side effects versus other ROS1 TKIs.
“As previously reported, the selectivity of taletrectinib for ROS1 over TrKB may explain the lower rates and narrower spectrum of neurologic side effects versus other ROS1 TKIs.20”
From Taletrectinib in <i>ROS1</i> + Non–Small Cell Lung Cancer: TRUST (2025) · cites this paper as [20]
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Taletrectinib in <i>ROS1</i> + Non–Small Cell Lung Cancer: TRUST
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- 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, C. M., & Zhou, C.
- Affiliations
- Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China
- Tongji University (CN)
- Central South University (CN)
- First Affiliated Hospital of Zhengzhou University (CN)
- Tumor Hospital of Guangxi Medical University (CN)
- Henan Cancer Hospital (CN)
- Sichuan University (CN)
- Shandong Tumor Hospital (CN)
- First Affiliated Hospital of Xiamen University (CN)
- Peking University Cancer Hospital (CN)
- First Hospital of China Medical University (CN)
- Guangdong Pharmaceutical University (CN)
- First Affiliated Hospital of Guangdong Pharmaceutical University (CN)
- Jiangsu Province Hospital (CN)
- Fujian Provincial Cancer Hospital (CN)
- AnHeart Therapeutics, New York, NY
- Vanderbilt-Ingram Cancer Center (US)
- Corresponding author
- Zhou, Caicun
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2024-08-01
- Volume
- 42
- Issue
- 22
- Pages
- 2660-2670
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC11272140
- OpenAlex
- W4399260107
- Cited by
- 40
- References
- 19
- Citations by year
- 2026: 14 · 2025: 23 · 2024: 3
- FWCI
- 11.62
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Journal of Clinical Oncology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- taletrectinib, ROS1-positive non-small cell lung cancer, ROS1 tyrosine kinase inhibitors, intracranial objective response rate, treatment-emergent adverse events, neurological adverse events, Chinese patients, progression-free survival
- MeSH terms
- Crizotinib, Progression-Free Survival, Tyrosine Kinase Inhibitors, East Asian People, Adult, Aged, Carcinoma, Non-Small-Cell Lung, China, Female, Humans, Imidazoles, Lung Neoplasms, Male, Middle Aged, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Pyridazines, Protein Kinase Inhibitors, Young Adult
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