KEY TAKEAWAYS
- The TRUST-I phase 3 study analyzed the efficacy and safety of taletrectinib in pts with patients with ROS1+ NSCLC.
- The study assessed IRC-confirmed cORR, DoR, DCR, PFS, and safety. Pooled analysis included pts from other trials for ORR, PFS, and safety.
- Taletrectinib exhibited high response rates, a prolonged PFS, robust intracranial activity, and activity against G2032R.
Taletrectinib is a promising treatment option for patients (pts) with ROS1+ NSCLC (n = 109). This potent and next-generation CNS-active ROS1 tyrosine kinase inhibitor (TKI) with selectivity over TRKB demonstrated significant clinical efficacy and was well tolerated by pts regardless of their pretreatment status with crizotinib (CRZ). With approximately 1.5 years of follow-up, it is clear that taletrectinib is a powerful and effective treatment.
The TRUST-I study demonstrated the efficacy and safety of taletrectinib in two cohorts: ROS1 TKI-naïve and CRZ-pretreated. Both cohorts were administered taletrectinib 600 mg QD. The study endpoints included IRC-confirmed ORR, DoR, disease control rate (DCR), PFS, and safety. A pooled ORR, PFS, and safety analysis, which had pts from further clinical trials, was also performed. The TKI-naïve pts (n = 67) had a median follow-up of 18.0 months, while CRZ-pretreated pts (n = 42) had 16.9 months. TKI-naïve patients had a cORR of 92.5%, while CRZ-pretreated patients had 52.6%. Median DoR (mDoR) and mPFS were not achieved. In pts with G2032R, the ORR was 80.0%, while the intracranial-ORR was 91.6%.
As per pooled analysis- phase I study for TKI-naïve patients, the ORR was 89.5%, whereas, for CRZ-pretreated patients, it was 50.0%, mPFS was 33.2 mo and 9.8 mo. Among the 178 patients treated at 600 mg QD, 92.7% encountered treatment-emergent adverse events (TEAEs), majorly grade 1–2 (64.0%). The most typical TEAEs were raised AST (60.7%), augmented ALT (55.6%), and diarrhea (55.6%). Neurological TEAEs like dizziness (18.5%) and dysgeusia (12.4%) were relatively low, and discontinuations due to TEAEs were minimal (3.4%). Upon further follow-up, the researchers observed that taletrectinib treatment exhibited high response rates, a prolonged progression-free survival period, robust intracranial activity, and activity against G2032R. In addition, the safety profile of this treatment was tolerable, with a low incidence of neurological adverse events.
Source: https://oncologypro.esmo.org/meeting-resources/european-lung-cancer-congress/updated-efficacy-and-safety-of-taletrectinib-in-patients-pts-with-ros1-non-small-cell-lung-cancer-nsclc
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04395677
Li, W., Li, K., Fan, H., Yu, Q., Wu, H., Wang, Y., Meng, X., Wu, J., Wang, Z., Liu, Y., Wang, X., Qin, X., Lu, K., Zhuang, W., He, S., Jänne, P.A., Seto, T., Ou, S.I., Zhou, C. Journal of Thoracic Oncology (2023)
