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Taletrectinib confirms its safety and efficacy in patients with ROS1+ non-small cell lung cancer

With additional follow-up of the TRUST-I study, taletrectinib continued to demonstrate meaningful efficacy outcomes with high response rates, prolonged progression-free survival and robust intracranial activity in patients with ROS1+ non-small cell lung cancer, both in ROS1 TKI-naïve and crizotinib-pretreated patients. Furthermore, taletrectinib was tolerable and had a low incidence of neurological adverse events.

Taletrectinib is a potent, next-generation, central nervous system-active, ROS1 tyrosine kinase inhibitor (TKI) with selectivity over TRKB. In previous reports from TRUST-I, taletrectinib showed meaningful clinical efficacy and was well tolerated in patients with ROS1+ NSCLC (N= 109) regardless of crizotinib pretreatment status. At ELCC 2023, updated efficacy and safety data with approximately 1.5 years of follow-up were presented.

Study design

TRUST-I is a multicentre, open-label, single-arm, phase II study with two cohorts: ROS1 TKI-naïve and crizotinib-pretreated patients. Patients in both cohorts received taletrectinib 600 mg once daily. All patients had locally advanced or metastatic NSCLC, were adults, had an ECOG performance status of 0-1 and had evidence of ROS1 fusion in tumour tissue. Key study endpoints included IRC-confirmed objective response rate (cORR), duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and safety. A pooled analysis of ORR, PFS, and safety including patients from additional clinical trials was also conducted.


In total, 109 patients were enrolled in TRUST-I. Of them, 67 were part of the TKI-naïve cohort and 42 of the crizotinib-pretreated cohort. Median age of the patients was 54 years, 40.4% were male, 74.3% had an ECOG PS of 1 and 22% had brain metastasis. Median follow-up was 18.0 months in TKI-naïve and 16.9 months in crizotinib-pretreated patients. cORR was 92.5% in TKI-naïve and 52.6% in crizotinib-pretreated patients, with a DCR of respectively 95.5% and 81.6%. Median time to response was 1.4 months in both cohorts and median DOR was not reached in either cohort. Furthermore, median PFS was not reached for the TKI-naïve patients and was reported at 9.8 months in the crizotinib-pretreated patients. The ORR in crizotinib-pretreated patients with a ROS1 G2032R resistance mutation was 80%. The intracranial ORR was reported at 91.7%. In a pooled analysis including patients from the TRUST-I phase II trial and two phase I trials conducted in the US and Japan (NCT02279433 and NCT02675491, mPFS was 33.2 months in TKI-naïve patients and 11.8 months in crizotinib-pretreated patients. In 178 patients treated at 600 mg QD, treatment-emergent adverse events (TEAEs) were mostly of grades 1 and 2, transient and reversible. TEAEs led to dose reductions or treatment discontinuation in respectively 20.2% and 5.1% of patients. The most common TEAEs were increased AST (70.8%), increased ALT (64.0%), and diarrhoea (61.2%). The incidence of neurological TEAEs was low and the majority was of grade 1.


Taletrectinib continued to demonstrate meaningful efficacy outcomes in both ROS1-TKI naïve and crizotinib-pretreated NSCLC patients. Furthermore, a high intracranial ORR was observed, regardless of line of therapy, and taletrectinib demonstrated tolerable safety.


Li W, et al. Updated Efficacy and Safety of Taletrectinib in Patients (pts) with ROS1+ Non-Small Cell Lung Cancer (NSCLC). Presented at ELCC 2023; Abstract 14MO.

Speaker Wei Li

Wei Li

Wei Li, MD, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Shanghai, China


See: Keyslides

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