Dr Liu on Updated Efficacy and Safety Data With Taletrectinib in ROS1+ NSCLC

"TRUST-II is a global study, and TRUST-I [was conducted] in the Chinese population. It's reassuring to see that the survival curves and the response rates [with taletrectinib] are all very similar between [these trials], as well as specifically [durable] in TRUST-II."

Geoffrey Liu, MSc, MD, a senior scientist at Princess Margaret Cancer Centre and a professor in the Epidemiology Division at Dalla Lana School of Public Health of the University of Toronto, shared updated efficacy and safety data from the global phase 2 TRUST-II trial (NCT04919811) investigating taletrectinib (Ibtrozi) in patients with ROS1-positive non–small cell lung cancer (NSCLC).

These results, which were presented during the 2025 IASLC World Conference on Lung Cancer, demonstrated sustained durability of responses with taletrectinib after additional follow-up in both TRUST-II and the phase 2 TRUST-I trial (NCT04395677), Liu reported.

For patients in TRUST-II who had not previously been treated with a ROS1 TKI (n = 54), the confirmed objective response rate (cORR) was 85.2% at a median follow-up of 20.5 months. Importantly, the median progression-free survival (PFS) was not yet reached, with the longest observed PFS at 31.6 months and ongoing. Similarly, the median duration of response (DOR) was also not yetreached, with the longest DOR observed at 30.4 months and continuing. Based on Kaplan-Meier estimates, 74.0% of patients achieved a DOR of at least 12 months, and 68% achieved at least 18 months. Intracranial responses were also significant, with 66.7% of patients with brain metastases (n = 9) achieving a response.

In TKI-pretreated patients (n = 47), taletrectinib produced a cORR of 61.7% at a median follow-up of 20.4 months. The median PFS was 11.8 months, and the median DOR was 19.4 months. Among those with brain metastases (n = 16), 56.3% achieved an intracranial response.

Pooled safety data from both studies confirmed taletrectinib’s favorable safety and tolerability profile, with no new safety signals observed, Liu stated. Common adverse effects like diarrhea, nausea, and dizziness were transient and manageable, often resolving within a few days to a week and rarely necessitating dose reductions or permanent discontinuations.

Liu emphasized the much lower proportion of patients experiencing TREK-related adverse effects such as dizziness and dysgeusia, which contributes to the drug’s overall tolerability. The extended follow-up, particularly the unreached medians for PFS and DOR in the first-line TKI-naive setting, provides significant reassurance regarding the drug's utility, he added. The similarity in survival curves and response rates between the global TRUST-II trial and the TRUST-I trial—the latter of which was conducted in a Chinese population—further supports the broad applicability of these efficacy findings, he concluded.