With approximately 3 years of follow-up, TKI-naive patients with ROS1+ NSCLC experienced long-term benefits with taletrectinib.
Taletrectinib (Ibtrozi) demonstrated high and durable response rates in TKI-naive patients with ROS1-positive non–small cell lung cancer (NSCLC), according to data from a pooled analysis of the phase 2 TRUST-I (NCT04395677) and TRUST-II (NCT04919811) trials presented during the
At the August 31, 2025, data cutoff, patients included in the pooled analysis (n = 157) achieved a confirmed overall response rate (ORR) of 89.8% (95% CI, 84.0%-94.1%) and an intracranial ORR (IC-ORR) of 76.5% (95% CI, 50.1%-93.2%) in evaluable patients (n = 17). At a median follow-up of 35.5 months, the median duration of response (DOR) in the pooled efficacy population (n = 141) was 49.7 months (95% CI, 38.6-not reached [NR]). The median progression-free survival (PFS) and overall survival (OS) among TKI-naive patients (n = 157) were 46.1 months (95% CI, 31.8-NR) and NR (95% CI, 47.8-NR), respectively.
“These data support taletrectinib as an effective, durable, and tolerable treatment option for patients with advanced ROS1-rearranged NSCLC who have not received a prior ROS1 TKI,” Lyudmila A. Bazhenova, MD, a medical oncologist and professor of medicine at UC San Diego Health, said during the presentation.
TRUST-I was conducted in China and TRUST-II was a global study.1 In order to be included in the studies, patients needed to have locally advanced or metastatic NSCLC with a ROS1 fusion, be at least 18 years old, and have an ECOG performance status of 0 or 1. Patients with brain metastases were permitted to enroll if the metastases were stable.
Both studies included TKI-naive and TKI-pretreated cohorts. All patients received taletrectinib at 600 mg every day. The efficacy population that was reported in the presentation included TKI-naive patients from TRUST-I and TRUST-II with at least 1 measurable baseline lesion per RECIST 1.1 criteria per independent review committee (IRC) who received taletrectinib at 600 mg. The safety population included patients in both the TKI-naive and TKI-pretreated cohorts of the 2 studies (n = 363).
The primary end point was ORR per IRC. Key secondary end points included DOR, PFS, OS, IC-ORR, and safety.
At baseline, the median age in the pooled efficacy population was 57 years (range, 26-83). Most patients were female (55.4%), Asia (87.9%), had stage IV disease (91.1%), had an ECOG performance status (73.9%), were never smokers (65.0%). Patients who received prior chemotherapy (19.1%) and those with brain metastases (23.6%) were also reported.
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).
In terms of safety, the most common any-grade treatment-emergent adverse effects (TEAEs) included increased aspartate aminotransferase levels (71.9%), increased alanine aminotransferase levels (68.3%), and diarrhea (64.5%). The rates of neurologic TEAEs were low and these events were primarily grade 1 or 2. TEAEs leading to dose interruptions (42.7%), reductions (31.3%), and discontinuation (8.5%) were all reported.
“With longer follow-up, we did not see any new safety signals, and safety was consistent between the integrated safety population and TKI-naive patients,” Bazhenova said. “To the best of our knowledge, this represents the highest ORR [as well as] the longest DOR and PFS reported to date for an FDA-approved ROS1 TKI in this patient population. This presentation adds 10 months of additional follow up since the last report, and taletrectinib continues to demonstrate management a manageable safety profile and low rate of neurologic adverse event.
Disclosures: Bazhenova is an independent contractor for AbbVie, AnHeart Therapeutics, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Genentech, Johnson & Johnson, Merck, Natera, Nuvalent, Pfizer, Revolution Medicines, Summit, and Taiho Oncology.
