Dr Mok on the Efficacy of Taletrectinib in ROS1+ NSCLC

Tony S. K. Mok, BMSc, MD, FASCO, Li Shu Fan Medical Foundation Endowed Professor, chairman, Department of Clinical Oncology, Chinese University of Hong Kong, discusses efficacy findings from a pooled analysis of the phase 2 TRUST-I (NCT04395677) and TRUSTII (NCT04919811) trials investigating taletrectinib (AB-106) in advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC).

This pooled analysis showed the efficacy of the second-generation ROS1 TKI taletrectinib in patients with ROS1-positive NSCLC. In the TKI-naive cohort, the confirmed overall response rate (cORR) with taletrectinib was 88.8% (95% CI, 82.8%-93.2%). In total, 20% of patients in this cohort had received prior chemotherapy. Additionally, the median progression-free survival (PFS) was 45.6 months (95% CI, 29.0-not reached [NR]), and the median duration of response was 44.2 months (95% CI, 30.4-NR), highlighting the long-term benefit of this agent, Mok says.

Among patients in the TKI-pretreated cohort, the cORR was 55.8% (95% CI, 46.1%-65.1%). In total, 37% of the patients in this cohort had received prior chemotherapy. The study also provided notable insights into outcomes among patients harboring the G2320R resistance mutation, Mok emphasizes. Of the 13 TKI-pretreated patients who expressed this mutation, 8 responded to treatment with taletrectinib. This translated to a cORR of 61.5% (95% CI, 31.6%-86.1%). Furthermore, the median PFS was 9.7 months (95% CI, 7.4-12.0), and the median DOR was 16.6 months (95% CI, 10.6-27.3) in all TKI-pretreated patients.

These efficacy findings underscore the efficacy of taletrectinib within the broader context of ROS1-targeted therapy, Mok explains. Although the TKI crizotinib (Xalkori) generated notable PFS outcomes in earlier studies of patients with ROS1-positive NSCLC, second- and third-generation TKIs, such as entrectinib (Rozlytrek) and lorlatinib (Lorbrena), have also demonstrated enhanced efficacy, he says. No head-to-head comparisons of these agents have been conducted; however, newer second-generation TKIs, including taletrectinib, likely offer superior PFS, ORR, and central nervous system efficacy, he reports.

Notably, in the pooled analysis of TRUST-I and TRUST-II, taletrectinib led to an intracranial ORR of 76.5% (95% CI, 50.1%-93.2%) in TKI-naive patients. These data reinforce the agent’s potential utility as a first-line therapy for patients with ROS1-positive NSCLC, particularly those with brain metastases, Mok concludes.

The most common treatment-related adverse effects (TEAEs) were elevated liver enzyme levels and gastrointestinal issues. Neurologic TEAEs included dizziness in 21.1% of patients and dysgeusia in 14.5% of patients; most neurologic TEAEs were grade 1.