Updated data from the phase 2 TRUST-II trial, presented at the 2024 IASLC World Conference on Lung Cancer, demonstrate that taletrectinib, a next-generation ROS1 tyrosine kinase inhibitor (TKI), induces robust overall and intracranial responses in patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). The efficacy was observed regardless of prior TKI exposure and geographic region.
Consistent Efficacy in TKI-Naive and TKI-Pretreated Patients
In TKI-naive patients (n = 54), taletrectinib produced a confirmed overall response rate (cORR) of 85.2% (95% CI, 72.88%-93.38%) at a median follow-up of 15.8 months. Among patients previously treated with a ROS1 TKI (n = 47), the cORR was 61.7% (95% CI, 46.38%-75.49%) at a median follow-up of 15.7 months.
"With the full enrollment of patients in this geographically diverse region, we were able to demonstrate meaningful efficacy in both TKI-naive and TKI-pretreated patients with ROS1-positive NSCLC," said Dr. Geoffrey Liu, lead study author and a senior scientist at Princess Margaret Cancer Centre in Ontario, Canada.
Intracranial Response
Assessment of intracranial responses among patients with measurable baseline brain metastases showed an intracranial ORR (IC-ORR) of 66.7% (95% CI, 29.93%-92.51%) in the TKI-naive group (n = 9). For TKI-pretreated patients (n = 16), the IC-ORR was 56.3% (95% CI, 29.88%-80.25%).
TRUST-II Trial Design
The single-arm, open-label, multicenter study enrolled patients with locally advanced or metastatic NSCLC who displayed evidence of a ROS1 fusion and had an ECOG performance status of 0 or 1. Patients were divided into TKI-naive and TKI-pretreated cohorts, receiving taletrectinib at 600 mg once daily in 21-day cycles. The primary endpoint was cORR per RECIST 1.1 criteria, assessed by an independent review committee (IRC).
Safety Profile
The median duration of exposure to taletrectinib was 8.4 months. Treatment-emergent adverse effects (TEAEs) leading to dose reduction occurred in 37.1% of patients, with 16.4% due to elevated liver enzymes. TEAEs leading to treatment discontinuation were reported in 7.5% of patients. No TEAEs leading to death were reported.
The most common TEAEs reported in at least 15% of patients were increased alanine aminotransaminase (67.9%), increased aspartate aminotransaminase (67.3%), diarrhea (56.6%), and nausea (51.6%).
"The majority [of gastrointestinal toxicities] were grade 1 and actually quite self-limiting in nature," Dr. Liu stated. "In this case, dysgeusia and dizziness were practically all grade 1 in nature, and none of them were grade 3 [or higher]."
