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.

Results

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.

Conclusion

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.

Reference

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.