WCLC 2025 | Updated results of taletrectinib in ROS1+ NSCLC from TRUST-II

So the TRUST-II trial is a phase 2 trial of taletrectinib and ROS1-positive non-small cell lung cancer. TRUST-I is a similar study, but was conducted completely in China. TRUST-II was conducted and is being conducted globally at this point. There are two main cohorts that have been presented in the TRUST-II trial, initially presented in 2022, but now with additional follow-up time and for the first time ever time to event outcomes are being presented at this World Conference of Lung Cancer. The two cohorts consist of a TKI-naive cohort, as well as one that is TKI-pretreated with either crizotinib or entrectinib in this case. The taletrectinib dose is 600 milligrams every day for all of these patients. And the endpoints include the confirmed objective response rate with secondary outcomes of duration of response, progression-free survival, duration of survival intracranial response rates as well in this setting. So the trial originally had a total of 55 TKI-naive and 50 pre-treated patients in TRUST-II. And the safety analysis involves 171 patients in this particular setting. The trial population is actually quite similar to what has been previously described for ROS1 patients. Generally speaking, a majority are lifetime never smokers, they tend to be younger in age compared with other subpopulations of lung cancer patients in this setting. Approximately one-fifth to one-third of patients had previously received prior chemotherapy before, and about nearly a third of the population, the TKI-naive, and half the population in the TKI pretreated presented with brain metastasis. So the outcomes are actually very interesting. So the updated outcomes first confirms a confirmed objective response in the TKI naive population of 85%, which is quite high. And we present waterfall plots that show quite deep responses that are seen. But of importance is that we now are able to present a median progression-free survival and median duration response in this population, and essentially neither of these have been reached with a median follow-up of 20 months. On top of this, in the TKI pre-treated patients, the objective response rate was 62%, similar to what was presented last year. The median duration of response in this pre-treated group was 19.4 months, and the median progression-free survival is sitting at 11.8 months. The safety of taletrectinib is much better documented now. The main adverse events consist of GI side effects, which tend to be mild and self-limiting. They include nausea, vomiting, and diarrhea. and of importance, the neurologic adverse events that are associated with TRK inhibition as a side effect is actually quite low with a 15% rate of dysgeusia in grade 1 and 4.1 in grade 2 and a dizziness rate that’s quite similar at 15.2% in grade 1 and 2.3% in grade 2. Only 2.3% discontinued treatment due to treatment-related adverse events. So overall, the safety profile as well as the efficacy profile of the data in TRUST-II is first of all consistent with the much longer follow-up data in TRUST-I, which was a trial in the Chinese population. Safety signals are actually very similar, and efficacy signals at this point are mimicking that of the pooled analysis as well as that of the TRUST-I trial.

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