Dr Drilon on Efficacy Results With Taletrectinib in ROS1+ NSCLC

Alexander Drilon, MD, thoracic oncologist, chief, early drug development service, Memorial Sloan Kettering Cancer Center, discusses efficacy findings from an integrated analysis of the regional TRUST-I (NCT04395677) and global TRUST-II (NCT04919811) trials which investigated treatment with taletrectinib (AB-106) in patients with ROS1-positive non–small cell lung cancer (NSCLC).

Data from the pooled analysis were presented during the 2024 ESMO Congress, and showed that taletrectinib elicited high, durable responses and had favorable tolerability in the registrational cohorts, Drilon begins. Among the 160 patients with ROS1 TKI–naive NSCLC, the confirmed overall response rate (cORR) by independent review committee (IRC) assessment was 88.8% (95% CI, 82.8%-93.2%), he reports. At a median follow-up of 21.2 months, the median duration of response (DOR) was 44.2 months (95% CI, 30.4-not reached [NR]), with a 24-month DOR rate of 70.2% (95% CI, 59.9%-78.3%). Furthermore, the median progression-free survival (PFS) reached 45.6 months (95% CI, 29.0-NR), and the 24-month PFS rate was 63.9% (95% CI, 54.2%-72.1%), he adds.

In patients with measurable brain metastases (n = 17), the intracranial cORR was 76.5% (95% CI, 50.1%-93.2%), indicating strong activity against brain lesions. Notably, deep responses observed on the waterfall plot revealed substantial disease regression in the majority of patients treated with taletrectinib, Drilon notes.

When compared with earlier-generation ROS1 TKIs, such as entrectinib (Rozlytrek) or crizotinib (Xalkori), and even other next-generation TKIs like repotrectinib (Augtyro), taletrectinib demonstrated superior or comparable response rates, Drilon states. Importantly, the durability of response and PFS seen with taletrectinib marked a significant improvement over older TKIs, reflecting the advantage of using a more potent, next-generation ROS1 inhibitor as frontline therapy, he explains.

This strategy mirrors trends seen in EGFR-mutant and ALK fusion–positive lung cancer, where second- or third-generation TKIs have replaced earlier-generation agents in the first-line setting due to their ability to achieve more durable responses and longer PFS, Drilon says. The results reinforce taletrectinib’s potential to become a preferred option for ROS1-positive NSCLC, Drilon concludes.