Pooled data from the TRUST-I and TRUST-II studies indicate that taletrectinib (AB-106) provides substantial and long-lasting benefits for individuals with advanced ROS1-positive non-small cell lung cancer (NSCLC). The integrated analysis, presented at the 2024 ESMO Congress, showed high overall response rates and favorable tolerability in both TKI-naive and TKI-pretreated patients.
Efficacy in TKI-Naive Patients
In 160 patients who had not previously received ROS1 tyrosine kinase inhibitors (TKIs), taletrectinib achieved a confirmed overall response rate (cORR) of 88.8% (95% CI, 82.8%-93.2%) as assessed by an independent review committee (IRC). With a median follow-up of 21.2 months (range, 3.6-46.6), the median duration of response (DOR) was 44.2 months (95% CI, 30.4-NR), and the 24-month DOR rate was 70.2% (95% CI, 59.9%-78.3%). The median progression-free survival (PFS) was 45.6 months (95% CI, 29.0-NR), with a 24-month PFS rate of 63.9% (95% CI, 54.2%-72.1%). Among the 17 patients with measurable brain metastases, the intracranial cORR (IC-cORR) was 76.5% (95% CI, 50.1%-93.2%).
Efficacy in TKI-Pretreated Patients
For the 113 patients who had been previously treated with ROS1 TKIs, taletrectinib demonstrated a cORR of 55.8% (95% CI, 46.1%-65.1%) by IRC assessment. Notably, in the subgroup of patients with G2032R mutations (n = 13), the cORR was slightly higher at 61.5% (95% CI, 31.6%-86.1%). At a median follow-up of 21.0 months (range, 3.9-45.4), the median DOR was 16.6 months (95% CI, 10.6-27.3), and the 12-month DOR rate was 61.1% (95% CI, 46.3%-73.1%). The median PFS in this group was 9.7 months (95% CI, 7.4-12.0), and the 12-month PFS rate was 39.7% (95% CI, 29.6%-49.6%). In the 32 patients with measurable brain metastases, the IC-cORR was 65.6% (95% CI, 46.8%-81.4%).
Study Details
The TRUST-I study was a regional, open-label, single-arm, phase 2 trial conducted in China, while TRUST-II was a multicenter, open-label, single-arm, global phase 2 study. Both trials evaluated taletrectinib in patients with ROS1-positive NSCLC. The pooled analysis included patients who were either TKI-naive or pretreated, all of whom received taletrectinib at a dose of 600 mg once daily. The primary endpoint was cORR per IRC assessment, with secondary endpoints including IC-cORR, DOR, PFS, and safety.
Safety Profile
The median duration of exposure to taletrectinib was 11.1 months (range, 0.1-64.1). The most common treatment-emergent adverse events (TEAEs) occurring in at least 15% of patients (n = 337) included increased aspartate aminotransferase (72.1%), increased alanine aminotransferase (68.0%), diarrhea (63.2%), nausea (47.2%), and vomiting (43.3%). TEAEs led to dose reductions in 28.8% of patients and discontinuation of taletrectinib in 6.5% of patients.
Expert Commentary
According to the study authors, “Integrated analysis from the TRUST-I and TRUST-II studies establishes taletrectinib as a potential best-in-class ROS1 TKI for people living with advanced ROS1-positive NSCLC.” The data suggest that taletrectinib offers a favorable benefit-risk profile at the recommended phase 2 dose of 600 mg once daily.
