FDA Reviews Updated Taletrectinib Data in Advanced ROS1-Positive NSCLC
The FDA has accepted for review a supplemental application for taletrectinib in advanced ROS1-positive NSCLC, with a PDUFA date of January 4, 2027. Updated TRUST-I and TRUST-2 data showed high response rates, durable responses and no new safety signals.
The Food and Drug Administration has accepted for review the supplemental New Drug Application for taletrectinib in the treatment of advanced ROS1-positive non-small cell lung cancer. The application includes updated pooled data from the phase 2 TRUST-I and TRUST-2 trials, and a Prescription Drug User Fee Act target date of January 4, 2027 has been set for the application. Taletrectinib is currently approved under the brand name Ibtrozi for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC.
Both single-arm trials evaluated taletrectinib 600 mg administered once daily in adults with advanced ROS1-positive NSCLC, with confirmed objective response rate as assessed by an independent review committee as the primary endpoint. Updated findings in TKI-naive patients from the pooled TRUST-I and TRUST-2 data set (data cutoff: August 31, 2025; n=157) showed the confirmed objective response rate was 89.8% (95% CI, 84.0-94.1), with a median duration of response of 49.7 months (95% CI, 38.6, not reached). Median progression-free survival was 46.1 months (95% CI, 31.8, not reached), the intracranial response rate was 76.5% in patients with brain metastases (n=17), and median overall survival was not reached (95% CI, 47.8, not reached).
Among TKI-pretreated patients in the pooled analysis (n=113), the confirmed objective response rate was 55.8% (95% CI, 46.1-65.1), with a median duration of response of 16.6 months (95% CI, 10.7-24.9). Median progression-free survival was 9.7 months (95% CI, 7.6-12.0), the intracranial response rate was 65.6% in patients with brain metastases (n=32), and median overall survival was 29.8 months (95% CI, 23.2-46.0).
Long-term follow-up of the Chinese phase II TRUST-I trial, as reported in the Journal of Clinical Oncology, showed prolonged activity with taletrectinib in patients with ROS1-positive non-small cell lung cancer. In the multicenter trial, 173 patients had received taletrectinib at 600 mg once daily by August 2025, including 106 tyrosine kinase inhibitor-naive patients and 67 crizotinib-pretreated patients.
Among TKI-naive patients in TRUST-I, with a median follow-up of 51.0 months, the objective response rate was 90.3% (95% CI, 82.9%-95.3%), median duration of response was 49.7 months (95% CI, 41.3 months to not reached), median progression-free survival was 49.6 months (95% CI, 34.5 months to not reached), and median overall survival was not reached (95% CI, 41.6 months to not reached; 3-year overall survival = 65.3%). Among crizotinib-pretreated patients, with a median follow-up of 45.2 months, the objective response rate was 51.5% (95% CI, 38.9%-64.0%), median duration of response was 13.2 months (95% CI, 7.7-24.8 months), median progression-free survival was 7.6 months (95% CI, 5.5-12.0 months), and median overall survival was 25.6 months (95% CI, 19.2-31.9 months).
Among 8 TKI-naive patients with measurable baseline brain metastases in TRUST-I, the intracranial objective response rate was 87.5%. Among 16 crizotinib-pretreated patients with measurable baseline brain metastases, the intracranial objective response rate was 75.0%.
The most common adverse events were increased aspartate aminotransferase, increased alanine aminotransferase, diarrhea, nausea, and vomiting. Treatment discontinuations due to treatment-emergent adverse events were low at 8.5%, and the safety profile was consistent with prior reports, with no new safety signals being identified.