An sNDA with updated data for taletrectinib was accepted by the FDA for TKI-naive and pretreated advanced ROS1+ NSCLC
The FDA has accepted a supplemental new drug application (sNDA) that includes updated data for taletrectinib (Ibtrozi) in TKI-naive and TKI-pretreated patients with advanced ROS1-positive non–small cell lung cancer (NSCLC).1 The target action date is January 4, 2027.
The sNDA, which the
At the August 2025 data cutoff, the median duration of response (DOR) was 49.7 months (95% CI, 41.3-not reached [NR]), and the median progression-free survival (PFS) was 49.6 months (95% CI, 34.5-NR) in TKI-naive patients in TRUST-I (n = 103).1,3 The median DOR was NR in TKI-naive patients and was 19.4 months in TKI-pretreated patients in TRUST-II (n = 54).
The safety profile of the agent was felt to be consistent with prior reports, with no new documented adverse effects.1
“These longer-term data for [taletrectinib]—which show an impressive median DOR of more than four years in TKI-naive patients, mirrored by the PFS results and supported by a consistent safety profile—reinforce our belief that [taletrectinib] is becoming the new standard of care in advanced ROS1-positive NSCLC,” David Hung, MD, founder, president, and chief executive officer of Nuvation Bio, stated in a news release. “The breadth and maturity of these data give both patients and providers even greater confidence when selecting [taletrectinib].”
TRUST-I and TRUST-II are both single-arm studies evaluating taletrectinib for the treatment of adults with advanced ROS1-positive NSCLC in China (n = 173) and globally (n = 189), respectively.
Eligible patients included those at least 18 years old with locally advanced or metastatic NSCLC with a ROS1 fusion and an ECOG performance status of 0 or 1. Brain metastases did not serve as an exclusion criterion if they were stable. TKI-naive and TKI-pretreated patients were included in both trials and received taletrectinib at 600 mg every day.
The primary end point of both studies was confirmed objective response rate (ORR) as assessed by an independent review committee. Secondary end points included DOR, PFS, overall survival (OS), intracranial ORR (IC-ORR), and safety.3
The results revealed a confirmed ORR of 89.8% (95% CI, 84.0%-94.1%) and an IC-ORR of 76.5% (95% CI, 50.1%-93.2%) in evaluable patients with TKI-naive disease (n = 157; n = 17, respectively). The median PFS and OS among TKI-naive patients were 46.1 months (95% CI, 31.8-NR) and NR (95% CI, 47.8-NR), respectively.
Further stratified, the confirmed ORRs among TKI-naive patients in TRUST-I (n = 103) and TRUST-II (n = 54) were 90.3% (95% CI, 82.9%-95.3%) and 88.9% (95% CI, 77.4%-95.8%), respectively. The median PFS values were 49.6 months (95% CI, 34.5-NR) and NR (95% CI, 15.9-NR), respectively. The respective median OS values were NR (95% CI, 41.6-NR) and NR (95% CI, NR-NR).
The phase 3, placebo-controlled TRUST-IV trial (NCT07154706) is evaluating taletrectinib vs placebo as adjuvant therapy in approximately 180 adults with resected early-stage ROS1-positive NSCLC.1 The primary end point is investigator-assessed disease-free survival, and the primary completion date is estimated to be in 2030.
There is also the confirmatory randomized phase 3 TRUST-III trial (NCT06564324), which is evaluating taletrectinib vs crizotinib (Xalkori) in 194 patients in China with advanced ROS1-positive NSCLC without prior exposure to ROS1 TKIs.
