ISAL 2025 | A Phase III trial incorporating inotuzumab ozogamicin into frontline ALL treatment for young adults

Yes, I’m going to talk a little bit about that during the meeting. This trial was designed as a successor trial to our 104-03 trial where we implemented the use of a pediatric regimen. And we realized very early from the results of 104-03, the prior regimen, that early eradication of resistant disease is a very, very important prognosticator and that patients who achieve MRD negativity early have outstanding survival rates above 85%. So similar to the pediatric population, really. But the problem has been that only a small, about 35 to 40% of young adults achieve very early eradication of MRD with the standard agents that we use in the pediatric regimens. And therefore, we decided to incorporate one of the novel targeted antibodies, inotuzumab ozogamicin, into frontline treatment early in a randomized Phase III trial. And that was very important to be able to randomize these patients, as you’ll see, because what happened was that we were going along perfectly well on this trial, and it was almost fully accrued when our data safety monitoring board informed us that we had excess deaths in the experimental arm that were occurring later in treatment, not during or immediately following the inotuzumab ozogamicin, but later. And these were mostly septic deaths, possibly due to prolonged myelosuppression, potentially some sort of immune compromise in addition from the prior exposure to inotuzumab ozogamicin. And for that reason, our primary endpoint was not achieved in this trial. On the other hand, I’m happy to say that all patients, both in the randomized and non-randomized arms, did significantly better than in 104-03, potentially because we had better adherence and because we made some minor tweaks to the protocol to make it both potentially more effective and less toxic. So what we’re trying to do now is there does look like there is potentially a tail, an early plateau on the survival curve for the inotuzumab arm. There were fewer relapses on that arm. And so now our challenge is to try to make that safer, potentially still using inotuzumab ozogamicin, but not using it in the exact manner in which we did. And so we’ve designed a successor pilot trial to follow up on this with lower dosing of inotuzumab and later on the addition of blinatumomab, which has been shown to improve outcomes even in MRD negative setting from other trials not exactly the same kind of trial but in other trials of B-ALL that include younger adults so that’s our current plan.

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