Taletrectinib—a next-generation selective ROS1 TKI that is active in the central nervous system—demonstrated strong response rates in patients with ROS1-positive advanced or metastatic non-small lung cancer (NSCLC) in a global phase II trial. The overall response rate (ORR) in TKI-naïve patients was 85%, with an 88% ORR in Asian patients and 81% in other subgroups. Results were also promising in TKI-pretreated patients, with an ORR of 62%, including a 57% ORR in Asia and 65% in other regions.
“Of note, it appears that taletrectinib works as well in patients pretreated with either crizotinib or entrectinib,” said Geoffrey Liu, MSc, MD, Senior Scientist at Princess Margaret Cancer Center and Associate Professor of Medicine at the University of Toronto. “The efficacy and safety of taletrectinib in the global TRUST-II trial remains highly consistent with findings from the regional TRUST-I trial.”
Dr. Liu reported results from TRUST-II during a mini-oral abstract session at the 2024 World Conference on Lung Cancer.
The study assessed 55 patients who were TKI-naïve and 50 who had previously been treated with a ROS1 TKI. The mean age of patients was 57 years, 56% were female, and 47% were from Asia. Forty percent had prior chemotherapy and 45% had stable brain metastases. Nearly all (95%) had stage IV disease.
ORR was the primary endpoint. Secondary endpoints included duration of response (DOR), best overall response, time to response, intracranial ORR, disease control rate, progression-free survival (PFS), and safety. DOR and PFS were immature at the time of data cutoff.
Activity was also observed in individuals with CNS involvement. TKI-naive patients with measurable brain metastases at baseline had an intracranial ORR of 67%, while TKI-pretreated patients with brain metastases had an intracranial ORR of 56%.
The safety profile of taletrectinib was generally good, Dr. Liu said. About two-thirds of patients had asymptomatic elevations of liver enzymes, most grade 1 or 2, and about half had diarrhea, nausea, or other gastrointestinal toxicities, nearly all grade 1 and self-limited in nature.
Rates of neurologic adverse events, as seen in other ROS1 TKIs, were low, Dr. Liu said, with dysgeusia at 20% and dizziness at 17%. Nearly all were grade 1 and none were higher than grade 3.
The median exposure to taletrectinib was 8 months; 37% of patients had a treatment-emergent adverse event leading to a dose reduction. The most common events leading to dose reduction were elevated liver enzymes in 16% of patients. Only 7% of patients had an adverse event leading to treatment discontinuation and just 1% were treatment-related. No adverse events resulted in death.
“With full enrollment of patients in geographically diverse regions, taletrectinib continues to demonstrate meaningful efficacy in both TKI-naïve and TKI pretreated patients with ROS1 positive non-small cell lung cancer,” Dr. Liu said. “There were robust overall and intracranial responses with comparable efficacy between patients in Asia and other regions.”
As of November 2024, talerectinib is not yet FDA-approved.
