Dr Porter on the Potential Role for Taletrectinib in ROS1+ NSCLC

Jason Porter, MD, medical oncologist, hematologist, director, Lung Cancer Disease Research Group, West Cancer Center and Research Institute, discusses the potential role of the next-generation TKI taletrectinib (AB-106) in patients with ROS1-positive non–small cell lung cancer (NSCLC), according to data from the phase 2 TRUST-II trial (NCT04919811).

Interim results from the international, multicenter, open-label, single-arm TRUST-II trial were presented at the 2023 ESMO Congress, and showed that taletrectinib demonstrated robust and durable tumor responses. Confirmed overall response rates with the agent were 92.0% (95% CI, 74.0%-99.0%) and 57.1% (95% CI, 34.0%-78.2%) in evaluable patients who were TKI naive and TKI pretreated, respectively.

Furthermore, the intracranial overall response rates in patients with measurable brain metastases were 80% (95% CI, 28.4%-99.5%) in the TKI-naive population and 62.5% (95% CI, 24.5%-91.5%) in the TKI-pretreated population.

These data have clinical implications for reshaping treatment approaches in ROS1-positive disease, Porter begins, adding that the agent’s impact may be comparable to that of crizotinib (Xalkori) in ALK-positive NSCLC. Taletrectinib exhibits notable activity against G2032R mutations, which are associated with resistance to crizotinib and earlier ROS1 inhibitors, Porter explains. This extends the potential applicability of taletrectinib to patients who have previously progressed on crizotinib, he says.

Notably, another key feature of taletrectinib is its efficacy against central nervous system (CNS) involvement, which has the potential to address unmet needs associated with crizotinib, Porter adds. Although crizotinib demonstrates CNS activity, recent ALK inhibitors have showcased improved efficacy in the CNS, he details. Taletrectinib shows similarly improved activity in patients with ROS1-mutant disease, potentially becoming a preferred choice for its enhanced CNS penetration, Porter states.

The ability to target the G2032R resistance mutation combined with increased CNS efficacy positions taletrectinib as a promising candidate for patients with ROS1 mutations who are at a higher risk of CNS disease, Porter emphasizes. These observed benefits could position taletrectinib as a prospective first-line agent for patients with ROS1-positive NSCLC in the future, he says.

In addition to taletrectinib's promising efficacy, it is important to consider potential toxicities associated with this agent, particularly neurotoxicity or CNS toxicity, Porter continues. However, taletrectinib was developed, in part, to overcome some of the CNS toxicity observed with crizotinib and entrectinib (Rozlytrek), he notes. Despite originating in a small patient population, the encouraging data from TRUST-II underscore the value of taletrectinib as a potential option for patients with ROS1-positive NSCLC in need of an effective and safe treatment, Porter concludes.