Clinical Summary:

• Updated results from the phase 2 TRUST-I and TRUST-II trials demonstrate that taletrectinib demonstrates high systemic and intracranial efficacy with prolonged disease control in TKI-naive patients with ROS1-positive NSCLC. 
• These results support its role as a potential best-in-class frontline ROS1 inhibitor. 

Lyudmila Bazhenova, MD, University of California, San Diego, California, discusses updated results from the TRUST-I and TRUST-II trials evaluating taletrectinib among TKI-naive patients with ROS1-positive non-small cell lung cancer (NSCLC). 

Results demonstrated that taletrectinib continued to maintain durable response with tolerable safety and positions taletrectinib as a highly effective next-generation ROS1 inhibitor in this setting.

Dr Bazhenova presented these results at the American Association for Cancer Research (AACR) Annual Meeting in San Diego, California. 

Transcript:

Hi, I'm Dr Lyudmila Bazhenova, professor of medicine and thoracic medical oncologist at University of California, San Diego, Morris Cancer Center. At AACR in April of 2026, on behalf of my coinvestigators, I presented the results of taletrectinib in TKI-naive patients with ROS1-positive rearranged non-small cell lung cancer, which was an updated data from TRUST-I and TRUST-II studies.

We know that ROS1-positive rearranged non-small cell lung cancer happens in approximately 1 to 2 percent of patients with stage 4 lung cancer, and we have several approved agents for patients with that condition. One of the approved agents is taletrectinib, which is a next-generation, CNS active, selective ROS1 tyrosine kinase inhibitor. We know from the past presentation that this medication has intracranial activity as well as a very robust systemic activity. 

At the AACR, we presented updated efficacy data for taletrectinib with an extra 10 months of follow-up. The clinical trials that we highlighted are TRUST-I and TRUST-II, those are pivotal phase 2 trials. TRUST-I enrolled primarily in China, TRUST-II was a global trial, and both of those studies had a TKI-naive cohort. Patients were receiving taletrectinib at 600 mg once a day, and the primary end point of the study was IRC-assessed confirmed overall response rate.

If you look at the results of the study, we see confirmed overall response rate of 90% in TRUST-I study, 88.9 in TRUST-II study. We also looked at the pooled analysis because the studies had a very similar inclusion criteria, therefore, we could combine the data. Pooled analysis of 157 patients’ overall response rate was 89.8. Very important to highlight that we also recorded intracranial activity with intracranial confirmed overall response rate by modified RECIST 1.1 in a pooled analysis was 76.5%. Responses appeared to be durable with median duration of response of over 4 years. In a pooled analysis, median duration of response was 49.7 months. Also important to highlight that taletrectinib showed a fairly long progression-free survival in a pooled analysis of 46.1 months and at 4 years, 48.9% of the patients were still without progression. 

If you look separately on the same data from a TRUST-I trial there, the median PFS was 49.6 months. In TRUST-II because the follow-up is much shorter in TRUST-II, the median PFS was not reached. Median OS also was not reached. Four years overall survival rate was 58.4%, meaning 58.4% of patients were still alive on the TRUST-I and TRUST-II clinical trials.

We didn't see any significant additional safety signals. We know the toxicity profile of teletruxinib, which the five most common side effects are increase in AST, ALT, diarrhea, nausea, and vomiting, and majority of those adverse events are early grade, grade 1/2, the grade 1 incidence was very low. Also, important to highlight that we did not see significant amount of neurologic events. Dizziness was seen in about 18.5% of patients grade 1 and 2.8 and grade 2. There was no grade 3/4 dizziness. Dysgeusia was seen in about 13.5% of the patients in grade 1 and 2.2 and grade 2, and there is also no incidence of grade 3 dysgeusia.

In summary, this presentation shows that taletrectinib continues to express a high overall response rate, long duration of response, and long progression-free survival. To our knowledge, this is the highest reported ORR, DOR, and PFS for any of the currently approved ROS1 tyrosine kinase inhibitors.

Source:

Liu G, Nieva J, Bazhenova L, et al. Taletrectinib in tyrosine kinase inhibitor (TKI)-pretreated patients with ROS1+ non-small cell lung cancer (NSCLC): Updated data from TRUST-I and TRUST-II. Presented at AACR Annual. April 17 - 22, 2026; San Diego, California. CT244.