AACR 2025 | Early clinical activity of SENTI-202, a CD33/FLT3-selective logic-gated CAR-NK therapy, in AML

The study, it’s a first-in-human multicenter study of SENTI-202, which is a CD33 FLT3 selective off-the-shelf logic-gated CAR NK-cell therapy that’s being looked at in hematologic malignancies and with a special interest in AML, obviously. So there’s a lot to sort of unpack there in that title by itself. 

But the short version is that it is off-the-shelf, it’s an allogeneic product. It’s something that is a cellular product, which is collected from healthy donors, and in the process, these cells can then be engineered to recognize two, what I would say are well-validated targets in regards to the AML population and heme malignancy population, one of which is CD33 and the other one is FLT3, and engineering these cells to hopefully be able to recognize, attack, and destroy the cancer cells by virtue of recognizing that property and being primed to attack the cells based on the cells that possess those markers. 

The results that we have presented so far demonstrated that we have been able to give this product safely, which is of paramount importance, obviously, in early Phase I drug development. But in addition, even at the first dose level, we’ve been able to see activity and significant activity. Within the first cohort at the first dose level, two of the first three patients actually went into remission. And not only remission, but a deep remission, something we call measurable residual disease negative. So the therapy was very quickly shown to be effective, but also shown to induce deep remissions. With the second cohort of patients where we actually used the overall same schedule, but we did increase the number of cells that patients received with each infusion, and also demonstrating that the higher cell dose was very tolerable. No dose-limiting toxicities were seen throughout the study thus far, but in either of those first two cohorts. And in the second cohort, another two out of three patients also achieved a very deep remission status. And so, obviously, four out of the first six patients, very excited to see that. Overall, we’ve had five out of the first seven evaluable patients achieve a response. A fifth patient did achieve what’s considered to be a morphologic leukemia-free state, where under the microscope, so to say, they didn’t see any evidence of residual leukemia at that time. And so overall, seeing activity in these first several patients, which is quite encouraging. 

In addition to the deep remissions, the MRD negative remissions that we are seeing, it should be noted that we’re also seeing nice durability. Of the four patients that have achieved a composite CR and MRD negativity, those patients are also having durable remissions, in that we have follow-up of over eight months at the time of the data analysis for this patient population with durability continuing beyond the eight-month time frame. So it’s one thing to be effective. It’s also something different and next level in order to be able to provide durability of remissions for patients. And we’re very excited about that.

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