Dr Liu on the Utility 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 the interim analysis of the phase 2 TRUST-II trial (NCT04919811), which is investigating the use of taletrectinib (AB-106) in patients with ROS1-positive non–small cell lung cancer (NSCLC).

At the 2023 ESMO Congress, Liu expanded on data from the international trial, which indicated that in evaluable patients (n = 154), taletrectinib induced robust and durable tumor responses, with a confirmed overall response rate (cORR) of 92.0% in patients who were TKI naïve and 57.1% in patients who were TKI pretreated. Moreover, intracranial responses proved to be robust, at 80.0% and 62.5% in patients who were TKI naïve and TKI pretreated, respectively.

These data are beneficial, specifically within the TKI-naïve patient population, where ORRs consistently surpass 90%, Liu begins. Taletrectinib is generating exceptionally high efficacy, even when compared with the efficacy seen with TKIs such as crizotinib (Xalkori) or entrectinib (Rozlytrek), he emphasizes. Notably, these data continue to impress investigators, as both the median duration of response and the median progression-free survival (PFS) have not yet been reached, Liu states.

Investigators continue to witness robust activity of taletrectinib within the central nervous system, a domain of importance, he expands. For patients who have not received prior treatment, particularly those with non-irradiated tumors and measurable brain metastases, the intracranial response rate stands at 80%, Liu says. Every patient treated in TRUST-II has exhibited some degree of reduction in their brain lesions. This neurological effectiveness is an important criterion for any drug used in patients with brain metastases, as the utility of these agents hinges on their ability to act decisively within the brain, Liu emphasizes. 

Although established agents in the NSCLC treatment paradigm, such as crizotinib or entrectinib, are initially effective, the median PFS elicited with these drugs typically hovers around 1.5 years and may be lower in real-world scenarios, depending on various co-variables, Liu continues. Although this 1.5-year median PFS represents a significant improvement over the PFS obtained with chemotherapy and immunotherapy options, this number should be increased, he states. The next generation of TKIs holds promise and may lead to longer PFS akin to those seen with ALK inhibitors, Liu concludes.