Taletrectinib in ROS1+ Non-Small Cell Lung Cancer: TRUST

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• Non-small cell lung cancer (NSCLC) with ROS1 alterations represents a distinct molecular subtype.
• Tyrosine kinase inhibitors (TKIs) targeting ROS1 have improved outcomes, but resistance and CNS metastasis remain challenges.

Purpose of the Study:

• To evaluate the integrated efficacy and safety of taletrectinib, a next-generation ROS1 TKI, in patients with ROS1+ NSCLC.
• To assess taletrectinib's performance in both TKI-naïve and TKI-pretreated populations, including its central nervous system (CNS) activity.

Main Methods:

• Phase II, single-arm, open-label, multicenter trials (TRUST-I and TRUST-II) were conducted.
• Efficacy outcomes, including confirmed objective response rate (cORR) and intracranial (IC)-cORR, were pooled.
• Safety data were collected from all patients treated with taletrectinib 600 mg once daily.

Main Results:

• In TKI-naïve patients (n=160), cORR was 88.8% and IC-cORR was 76.5%.
• In TKI-pretreated patients (n=113), cORR was 55.8% and IC-cORR was 65.6%.
• Median progression-free survival (PFS) was 45.6 months for TKI-naïve and 9.7 months for TKI-pretreated patients. Most treatment-emergent adverse events were low-grade GI events and elevated liver enzymes.

Conclusions:

• Taletrectinib exhibits significant efficacy, including durable responses and robust CNS activity, in ROS1+ NSCLC.
• The drug demonstrates a favorable safety profile with low rates of severe adverse events and infrequent neurologic toxicities.
• Taletrectinib represents a promising therapeutic option for both TKI-naïve and TKI-pretreated patients with ROS1+ NSCLC.