Updated data from the global, multicenter, single-arm phase II TRUST-II trial, which were reported by Liu et al during the International Association for the Study of Lung Cancer (IASLC) 2024 World Conference on Lung Cancer (WCLC; Abstract MA06.03), continued to demonstrate robust overall and intracranial responses with the next-generation ROS1 tyrosine kinase inhibitor taletrectinib in patients with locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC), regardless of their prior tyrosine kinase inhibitor exposure status and geographic region.

Study Details

In this trial, patients were classified into either a ROS1 tyrosine kinase inhibitor–naive (up to one prior line of chemotherapy) or –pretreated (one prior ROS1 tyrosine kinase inhibitor and up to one prior line of chemotherapy) cohort. Both cohorts were administered 600 mg of taletrectinib once daily.

At the data cutoff date of June 7, 2024, 55 and 50 patients, respectively, were included in the tyrosine kinase inhibitor–naive and –pretreated cohorts. The overall population, in which safety was assessed, comprised 159 patients from both these and other heavily pretreated cohorts.

A total of 61.8% and 44.0% of the tyrosine kinase inhibitor–naive and –pretreated cohorts, respectively, were from Asia. Of these cohorts, 34.5% and 56.0% had baseline brain metastases. Prior anticancer chemotherapy was administered in 20.0% of the patients who underwent prior tyrosine kinase inhibitor therapy and 38.0% of those who did not. In the tyrosine kinase inhibitor–pretreated cohort, 80.0% of patients received crizotinib, and 20.0% were treated with entrectinib.  

The primary endpoint was the independent review committee–assessed confirmed objective response rate. Duration of response, progression-free survival, and safety were evaluated as key secondary endpoints.

Overall and Intracranial Response Rates

In the objective response–evaluable patients who did (n = 47; brain metastases: n = 16) and did not (n = 54; brain metastases: n = 9) undergo prior tyrosine kinase inhibitor therapy, the median durations of follow-up were 15.7 (range = 3.9–29.8 months) and 15.8 (range = 3.6–29.8 months) months, respectively.  

The confirmed overall and intracranial objective response rates were 85.2% and 66.7%, respectively, in the tyrosine kinase inhibitor–naive cohort. The confirmed overall objective response rates were found to be similar between the patients from Asia (n = 33; 87.9%) and those from other regions (n = 21; 81.0%).

The tyrosine kinase inhibitor–pretreated cohort demonstrated a confirmed overall objective response rate of 61.7% and an intracranial objective response rate of 56.3%. In patients from Asia (n = 21) vs other regions (n = 26), the confirmed objective response rate was 57.1% vs 65.4%, respectively.

Dr. Liu noted that, at the time of this analysis, the duration of response and progression-free survival data remained immature in both cohorts.

Safety Findings

Increased levels of alanine transaminase (67.9%; grade ≥ 3: 15.1%) and aspartate transaminase (67.3%; grade ≥ 3: 6.9%) were among the most frequently reported treatment-emergent adverse events. The most common gastrointestinal toxicities were diarrhea (56.6%; grade ≥ 3: 0.6%), nausea (51.6%; grade ≥ 3: 1.9%), and vomiting (33.3%; grade ≥ 3: 1.3%); according to Dr. Liu, most of these events were grade 1. He stated that nearly all the neurologic toxicities were grade 1 (any grade, dysgeusia: 19.5%; dizziness: 17.0%), and none were grade 3 or higher.

A total of 37.1% and 7.5% of patients were given a dose reduction or discontinued treatment because of a treatment-emergent adverse event. No treatment-related adverse events resulted in death.

“With full enrollment of patients in geographically diverse regions, we were able to demonstrate meaningful efficacy in both tyrosine kinase inhibitor–naive and –pretreated patients with ROS1-positive NSCLC,” Dr. Liu concluded. “The efficacy and safety of taletrectinib in the global TRUST-II trial remain highly consistent with findings from the regional TRUST-I trial.”

Geoffrey Liu, MD, MSc, of Princess Margaret Cancer Centre, University of Toronto, presented this abstract at the 2024 World Conference on Lung Cancer.   

Disclosure: Dr. Liu reported no conflicts of interest.