The trial is a study of a drug called IDRX-42, now it has a name, velzatinib. It was designed as a phase I dose escalation with then a dose expansion cohort. In the dose escalation they had studied doses of 120mg daily, capsule doses, all the way up to 600mg b.i.d. Somewhere between the trial they did convert the capsule formulation to a tablet formulation, so the 600mg correlated with a 300mg dose of the velzatinib. So after the dose escalation the dose expansion cohorts were in the first-line GIST setting, second-line GIST setting and then third line and beyond. Initially they had excluded other new drugs in the area for the third line and beyond and then they opened another cohort where they did allow patients who had been exposed to other new agents, like bezuclastinib, and there was another compound, NB003, that were allowed to enrol on the study after.

What’s being reported at ASCO 2026?

At ASCO this year we presented data on… there were two oral presentations. One of the oral presentations was specific to the first-line cohort and the second-line cohort data. So patients who were in the expansion cohorts for front-line, advanced or metastatic GIST patients, and also patients in the second-line after imatinib in the advanced or metastatic setting.

So we presented data that showed that the response rate in the first-line setting was 61% but unconfirmed responses up to 65%. The time to response was short and so far the responses look durable. In fact, initially all patients did have some amount of tumour reduction and 83% of patients still remain on study in that first-line cohort.

In the second-line cohort the responses were in the 40% range in the second-line setting and those patients there were also quite a few durable responses that have been seen. The progression free survival of the second-line cohort, I think there are around 48 patients in the second-line cohort presented, was around 13.7 months. The PFS for the first-line cohort has not been reached.

What was presented was also that this is a very tolerable agent. It’s more similar to imatinib in terms of its tolerability profile where there is some GI toxicity, there could be some patients with some cytopenias, but overall very well tolerated. The dose reductions that patients had to have were minimal.

What was also presented in ASCO this year was the ctDNA data showing how the ctDNA clearance with this agent corresponded across all lines of therapy. So that was presented this morning in the rapid orals, or actually in the oral session this morning, that the ctDNA across all mutation subsets, both primary, exon 11 and exon 9 for KIT-mutant GIST, and also the activation loop 17 and 18 secondary mutations and 13/14 secondary mutations of the ATP binding site all showed reduction in their ctDNA levels on therapy.

Some interesting data also came out of it that patients who shed less, where they have lower levels of ctDNA that is detectable in the blood, do seem to do well overall versus those that have more shedding. I think it could be a result of tumour bulk but what’s exciting to see is there is an active agent that has broad coverage.

What adverse events were found?

The adverse events, as I mentioned, it is very well tolerable. Patients can experience diarrhoea, some dysgeusia taste alterations, some GI discomfort. There is some neutropenia that has been reported. In general well tolerated, I don’t think we had any major toxicities that were not anticipated that we don’t see with the prior agents. We did monitor for liver functions and all labs and didn’t see a major issue with that.

What impact could these results have and what’s next?

Velzatinib, based on these excellent data, is already being studied in the second-line setting compared to sunitinib. So there is an ongoing phase III trial that compares velzatinib versus sunitinib in the second-line setting for advanced metastatic GIST that has progressed on imatinib or intolerable to imatinib. Patients do get crossover at the time of progression if they are on the sunitinib arm.

We are also planning a first-line study, a phase III first-line study, that compares velzatinib to imatinib that will be opening shortly, in a couple of months I assume, at least in a few sites which, for the first time since imatinib was approved is an agent going to be looked at in the front-line setting for advanced GIST. So that’s the future.