Dr Liu on the TRUST-II Trial of Taletrectinib in ROS1+ NSCLC

Stephen V. Liu, MD, associate professor, medicine, Georgetown University, director, Thoracic Oncology, head, Developmental Therapeutics, Georgetown Lombardi Comprehensive Cancer Center, discusses updated data from the phase 2 TRUST-II trial (NCT04919811) investigating taletrectinib (AB-106) in patients with ROS1-positive non–small cell lung cancer (NSCLC).

Efficacy findings from TRUST-II presented during the 2024 IASLC World Conference on Lung Cancer demonstrated durable overall and intracranial responses with the next-generation ROS1 TKI in patients with locally advanced or metastatic ROS1-positive NSCLC. The single-arm, open-label, multicenter study enrolled patients 18 years of age or older with locally advanced or metastatic NSCLC who displayed evidence of a ROS1 fusion, Liu details. Patients were divided into 2 cohorts: TKI-naive patients with no more than 1 prior line of chemotherapy (cohort 1) and patients pretreated with 1 prior ROS1 TKI and no more than 1 line of chemotherapy (cohort 2).

Taletrectinib is a potent, rationally designed ROS1 TKI engineered to address key limitations of earlier agents, such as entrectinib (Rozlytrek) or crizotinib (Xalkori), which often loses efficacy due to the emergence of resistance mutations in the ROS1 protein, Liu explains. Taletrectinib retains its activity against these resistance mutations, offering a twofold benefit: overcoming resistance in pretreated patients and potentially delaying the onset of resistance in TKI-naive patients, he says.

A defining advantage of taletrectinib is its selectivity, Liu notes. Although other next-generation TKIs, such as entrectinib and the next-generation ROS1 TKI repotrectinib (Augtyro), also target NTRK fusions, this dual activity introduces off-target adverse effects (AEs), including balance disturbances and impaired spatial orientation, Liustates. These AEs significantly affect quality of life, particularly in patients without NTRK-driven tumors, he adds. By avoiding this off-target activity, taletrectinib reduces these unwanted toxicities, as confirmed in the TRUST-II trial, Liu emphasizes.

With its potent activity against ROS1 and resistance mutations, along with a favorable safety profile, taletrectinib represents a significant advancement in targeted therapy for ROS1-positive NSCLC, particularly for patients requiring effective and tolerable treatment options, Liu concludes.