Taletrectinib for patients with ROS1+ non-small cell lung cancer: the global TRUST-II study
In the phase II TRUST-II study, the ROS1 tyrosine kinase inhibitor (TKI) taletrectinib demonstrated high overall and intracranial responses, with a favourable safety profile and low incidence of neurologic adverse events, in both TKI-naïve and TKI-pretreated patients with ROS1+ non-small cell lung cancer (NSCLC).
Taletrectinib, a highly potent, next-generation, CNS-active, selective ROS1 tyrosine kinase inhibitor (TKI), demonstrated high overall and intracranial (IC) response rates, prolonged progression-free survival (PFS), and activity against the ROS1G2032R acquired resistance mutation with favourable tolerability in the regional TRUST-I study. At WCLC, updated results in TKI-naive and TKI-pretreated patients from the global pivotal phase II TRUST-II study were presented.
Study design
TRUST-II, a global, multicentre, single-arm study of taletrectinib (600 mg, once-daily) in adult patients with ROS1+ locally advanced or metastatic NSCLC, included 2 registrational NSCLC cohorts: 1) TKI naive, ≤1 line of chemotherapy, and 2) TKI pretreated, one prior ROS1 TKI and ≤1 line of chemotherapy. All patients had an ECOG performance status of 0 or 1. Primary endpoint was confirmed objective response rate (cORR) by independent review committee per RECIST v1.1. Key secondary endpoints included duration of response (DOR), PFS, and safety.
Results
In total, 159 patients were enrolled. Median age of the patients was 57 years, 56% were female, 46.5% were Asian and 56.6% never smoked. Among cohorts 1 (n=55) and 2 (n=50), baseline brain metastases were observed in 34.5% of TKI-naive and 56% of TKI-pretreated patients; 20% of TKI-naive and 38% of TKI-pretreated patients received prior anticancer chemotherapy. In TKI pretreated patients, 80% received prior crizotinib and 20% received prior entrectinib.
In TKI-naive patients, the confirmed objective response rate (cORR) was 85.2% and intracranial objective response rate (IC-ORR) was 66.7%. In TKI-pretreated patients, cORR was 61.7% and the IC ORR was 56.3%. Median exposure of taletrectinib was 8.4 months. The most common treatment-emergent adverse events (TEAEs) in TRUST-II were increased ALT (67.9%), increased AST (67.3%), and diarrhoea (56.6%). Rates of neurologic TEAEs were low (dysgeusia [19.5%]; dizziness [17.0%]; none were grade ≥3). In total, 37.1% of patients had a TEAE leading to a dose reduction. No treatment-related AE led to death.
Conclusion
With full enrollment of patients in geographically diverse regions, taletrectinib continues to demonstrate meaningful efficacy in both TKI-naive and TKI-pretreated patients with ROS1+ NSCLC. Taletrectinib demonstrated a favourable safety profile, with a low rate of treatment discontinuation due to TEAEs. The efficacy and safety of taletrectinib in the global TRUST-II trial remains highly consistent with findings from the regional TRUST-I trial.
Reference
Liu G, et al. Efficacy and Safety of Taletrectinib in Patients with ROS1+ Non-Small Cell Lung Cancer: The Global TRUST-II Study. Presented at WCLC 2024; Abstract 1752.