In a pooled analysis of the phase II TRUST-I and TRUST-II trials reported in the Journal of Clinical Oncology, Pérol et al found that the oral, potent, CNS-active, selective, next-generation ROS1 tyrosine kinase inhibitor (TKI) taletrectinib was highly active in ROS1-positive advanced or metastatic non–small cell lung cancer (NSCLC).
Study Details
TRUST-I was a Chinese study with two cohorts: TKI-naive patients and patients in whom previous crizotinib failed. TRUST-II was an international study with two cohorts: TKI-naive patients and patients previously treated with crizotinib or entrectinib. The safety population included patients who had received taletrectinib at 600 mg once daily in 21-day cycles until disease progression or unacceptable toxicity. The primary endpoint of the analysis was independent review committee–assessed confirmed objective response rate.
Key Findings
The pooled efficacy-evaluable population included 273 patients from TRUST-I and TRUST-II.
Among 160 TKI-naive patients, objective responses were observed in 142 (82%), including complete response in 8. Median duration of response was 44.2 months (95% confidence interval [CI] = 30.4 months to not reached). Median progression-free survival was 45.6 months (95% CI = 29.0 months to not reached).
Among 113 TKI-pretreated patients, objective responses were observed in 63 (55.8%), including complete response in 5. Median duration of response was 16.6 months (95% CI = 10.6–27.3 months). Median progression-free survival was 9.7 months (95% CI = 7.4–12.0 months).
Among 13 patients with the ROS1 G2032R mutation, objective response was observed in 8 (61.5%).
Among patients with baseline measureable brain metastases, intracranial responses were observed 13 (76.5%) of 17 patients in the TKI-naive group and in 21 (65.6%) of 32 patients in the TKI-pretreated group. Median durations of intracranial response were 14.7 months (95% CI = 4.2–30.2 months) in TKI-naive responders and 11.9 months (95% CI = 6.9–23.4 months) in TKI-pretreated responders.
Among a total of 352 patients who received 600 mg of taletrectinib pooled across the clinical program, the most commonly reported adverse events of any grade were gastrointestinal events (88%) and elevated aspartate aminotransferase (72%) and alanine aminotransferase (68%), with most being grade 1. Neurologic adverse events were less frequent, including dizziness (21%) and dysgeusia (15%)—again, mostly grade 1. Adverse events leading to treatment discontinuation occurred in 6.5% of patients.
The investigators concluded, “Taletrectinib showed a high response rate with durable responses, robust intracranial activity, prolonged progression-free survival, favorable safety, and low rates of neurologic adverse events in TKI-naive and pretreated patients [with advanced ROS1-positive NSCLC].”
Caicun Zhou, MD, PhD, of the Department of Medical Oncology, East Hospital, Tongji University School of Medicine, Shanghai, China, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Nuvation Bio Inc. For full disclosures of the study authors, visit ascopubs.org.
