I will be discussing the efficacy and safety of taletrectinib in patients with ROS1 fusion non-small cell lung cancer as part of the TRUST-II study, specifically the subgroup of patients who were pretreated with entrectinib. Taletrectinib is a ROS1-targeting tyrosine kinase inhibitor that has very specific properties. First of all, it is very active in the brain and in the central nervous system. Secondly, it targets the G2032R resistance mutation and, third, it’s a selective ROS1 inhibitor with very few tricky side effects and adverse events.

The TRUST-II data was originally presented over a year ago but this is the subgroup of patients that were particularly pretreated with entrectinib. Entrectinib is another ROS1-targeting tyrosine kinase inhibitor that also has brain or CNS activity but is considered first generation. In this particular analysis we’re looking at a relatively small number of patients, ten patients, but a couple of important things have come out. First of all, the demographics of this population is similar to that of the larger ROS1 fusion population. Secondly of all, seven of these ten patients, or 70%, had brain metastasis at the time of entry into the study.

With this in mind, one patient ended up having a complete response, seven patients had a partial response and one additional patient had stable disease for a confirmed response rate of 80% and a disease control rate of 90%. This is all in the setting after entrectenib. Of the four patients that had measurable disease in the brain, two of them, or 50%, ended up having a confirmed response rate as well too. So it’s actually active to control brain metastasis in the setting of individuals who previously were on entrectinib as well.

In terms of safety, the overall safety signals were actually very similar to the larger study itself. The main side effects consisted of that of elevated liver enzymes, mostly grade 1 and a little bit of grade 2, with very few requiring a dose modification, and diarrhoea. The GI side effects tend to be very self limiting and last possibly just a few days on average in this setting, so otherwise very well tolerated. Importantly, unlike entrectinib, it does not appear to have the following side effects such as weight gain, visual changes or disturbances, and also in particular heart failure as well.

So overall in this TRUST-II trial it’s clear that taletrectinib works really well in both overall and intracranial efficacy after patients have received entrectinib. Also, importantly, the safety of this drug seems to be very well tolerated.

Overall the trial has a larger number of patients that we’re following at the moment but the key feature seems to be that there does not seem to be any difference at all between the patients previously treated with crizotinib, for which we have a lot of data, and the subgroup of patients treated with entrectinib. The drug itself is already available in the US and also available in Japan and China so there will be additional real-world data that will be coming out of their experiences as well.

What could be the implications of these findings?

First of all with taletrectinib being available in these countries a few things that we know about this drug is that it has significantly fewer adverse events, particularly [??] side effects than prior drugs such as repotrectinib and entrectinib. It also has a significantly longer median progression free survival and duration of response as well. So I believe that at this point it will take over in terms of the first-line use. Because of its benefit after entrectinib it will also take over in terms of the next drug to use in patients previously treated with both crizotinib and entrectinib, both in terms of the efficacy side but really importantly also in terms of the safety side.