The U.S. Food and Drug Administration (FDA) has approved taletrectinib for the treatment of adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).
ROS1-positive NSCLC is a rare and aggressive lung cancer that typically occurs in patients aged 50 years and older and who have never smoked. Brain metastases are common in patients with this condition and are the leading cause of disease progression.
Taletrectinib is an oral, central nervous system-active, selective ROS1 tyrosine kinase inhibitor.
TRUST Clinical Trial Program
The FDA approval follows positive results from the TRUST clinical trial program. Both TRUST-I and TRUST-II are phase 2, single-arm, pivotal studies evaluating taletrictinib in adults with advanced ROS1 positive NSCLC. The TRUST-I trial enrolled 173 patients in China and TRUST-II enrolled 164 patients globally. The primary endpoint was confirmed objective response rate (cORR) and key secondary endpoints were intracranial cORR, duration of response (DOR), progression-free survival, and safety.
In TRUST-I a cORR of 90% was achieved with taletrictinib in TKI-naïve patients and was built upon by a 85% cORR in TRUST-II. Median duration of response has not yet been reached in either trial. However, for TRUST-1, with a median follow-up for response of 40 months, the longest DOR observed is 46.9 months and is ongoing. For TRUST-II, with a median follow-up response of 19 months, the longest DOR observed is 30.4 months and ongoing.
Consistent results were also seen in patients previously treated with a ROS1 TKI. In TRUST-I, taletrictinib treatment achieved a cORR of 52% and median DOR of 13.2 months with a median follow-up for responses of 33 months in previously treated patients. In TRUST-II, taletrictinib treatment achieved a cORR of 62% and a median DOR of 19.4 months with a median follow-up for responses of 19 months as of October 2024.
Additionally, taletrictinib has demonstrated consistent intracranial responses in patients with measurable brain metastases at baseline. An intracranial response was achieved in 73% of TKI-naïve patients and 63% of TKI-pretreated patients.
The safety profile of taletrictinib has been favorable and generally well-tolerated. Most adverse events have been low grade, transient, and manageable. The most common adverse events have been diarrhea, nausea, vomiting, dizziness, rash, constipation, and fatigue.
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