SOHO 2026 | Phase II SUMMIT: bezuclastinib reduces symptoms and disease burden in systemic mastocytosis

So SUMMIT is the pivotal trial of bezuclastinib, which is, you know, a KIT D816V inhibitor that does not penetrate the blood-brain barrier, that has few, if any, off-target effects. It does inhibit wild-type KIT, but that’s about it, you know, wild-type KIT and the mutant KIT. So this is a very promising agent in development for systemic mastocytosis. SUMMIT is the pivotal trial of this agent in indolent and smoldering systemic mastocytosis. And, you know, an application has been filed with the FDA. We even have a PDUFA date later on this year. So, you know, SUMMIT looked at bezuclastinib versus placebo, you know, in the randomized phase. There was, of course, a dose-finding phase before that. And there is an extension phase after the randomized phase. But, you know, obviously all eyes are on the randomized phase. And this was bezuclastinib versus placebo, 100 milligram daily of bezuclastinib versus placebo. Now, like the PIONEER trial of avapritinib, you know, which we can use as a bit of a reference, the one that led to avapritinib’s approval in indolent SM, this too required a certain symptom threshold, you know, that patients had to meet in order to go on to the trial. And they had to be on a stable regimen of at least two best supportive care medications. So in that sense, very similar to the PIONEER trial. And, you know, what’s important is the dose, again, is 100 milligrams a day here, a little bit different from advanced, which is 150 for bezuclastinib.

So SUMMIT was, again, presented at ASH last year, 2025, a very positive trial in terms of the symptom reduction, which is the primary endpoint. This trial does use a novel symptom questionnaire, a novel symptom assessment tool. It’s called the MS2D2. I think it is Mastocytosis Symptom Severity Daily Diary, MS2D2. It’s a proprietary tool, you know, that belongs to Cogent. So that’s the tool that was used. So the primary endpoint was easily met, you know, with the symptom reduction. And I want to say, at least at the 24-week data, it was around minus 24 in the bezuclastinib arm and minus 15 in the placebo arm. And this is talking about the absolute TSS. So we’re talking about the reductions. But, you know, what’s perhaps even more impressive with bezuclastinib is that, you know, you also get these profound reductions in the markers of disease burden. So the tryptase, the KIT D816V VAF, as well as the bone marrow mast cell percentage, you know, really they dramatically go down. In fact, 55% of patients no longer met WHO criteria for an SM diagnosis. So you’ve got an agent that greatly improves symptoms and, you know, greatly reduces the markers of mast cell burden. And what was unique to bezuclastinib, I don’t recall this being shown with avapritinib, is that there was a correlation between the symptom reduction and the disease burden markers going down. So, you know, proof of hitting the target and that correlating with symptom improvement. So I think those are really the main takeaways from SUMMIT at 24 weeks. And what we showed at SOHO is really that these benefits were maintained and improved at week 48. So this was an encore of the 48-week data that was presented at the Quad AI meeting, the allergy meeting in the US this year. And so really at 48 week, like we’ve seen with avapritinib, really deepening of the responses, no new safety signals, and just, you know, with time responses improving. And also those, the extent of reduction of those three things, the tryptase, the KIT VAF, the bone marrow mast cells continuing to deepen.

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