FDA Approval of Taletrectinib for ROS1+ NSCLC: Dr. Liu Weighs In

Stephen Liu, MD, Director of Thoracic Oncology at Georgetown University, joined Lung Cancers Today to share his insights on the recent FDA approval of taletrectinib for locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC).

“This is an important advance,” Dr. Liu noted, explaining that the FDA approval of taletrectinib was based on the TRUST-I and TRUST-II studies.

The two multicenter, single-arm, open-label clinical trials evaluated the efficacy of the drug in 157 patients who were naïve to treatment with a ROS1 tyrosine kinase inhibitor (TKI) and 113 patients who had received one prior ROS1 TKI.

These two studies showed that taletrectinib had “remarkable activity” in patients who had received previous treatment with a ROS1 TKI, Dr. Liu said, noting that there were “even more impressive outcomes” in patients who were treatment-naïve.

In TRUST-I, the overall response rate (ORR) was 90% for treatment-naïve patients and 52% for those who received previous TKI treatment. In TRUST-II, the ORR was 85% in those who were treatment-naïve, compared with 62% in those who received previous TKI treatment.

A duration of response of 12 months or longer was demonstrated among responders in both trials, measuring 72% and 63%, respectively.

“We’re seeing high response rates and this enters a field where we have other very active ROS1 TKIs,” Dr. Liu said. “Our first drugs approved were crizotinib and entrectinib. Those agents are clearly providing benefit[s] to many patients. Repotrectinib was most recently approved here, with very high response rates. But the challenge has always been with toxicity.”

However, when it comes to those ROS1 TKIs, Dr. Liu explained that “the challenge has always been with toxicity.”

“There was notable toxicity with regard to neurotoxicity, specifically proprioception,” Dr. Liu said. “This has to do with the fact that many of these ROS1 inhibitors like entrectinib and repotrectinib also target NTRK. Those drugs are approved for NTRK-fusion positive cancers, but when you target NTRK, you do increase toxicity.”

He explained that these toxicities “impact the quality of life and our ability to deliver these drugs for long periods of time,” noting that taletrectinib “is important because [of] its TrKB selectivity.”

“By focusing its activity and minimizing some of those on-target TrK toxicities, we can see less toxicity from a neuro standpoint and better tolerability, which I think translates to being able to continue this drug for longer,” Dr. Liu said. “To me, taletrectinib, emerges as potentially a preferred option, where [it’s] available for most patients.”