ASH 2024 | An ongoing Phase I study of AZD0486, a novel CD19xCD3 bispecific antibody, in R/R DLBCL

Yeah, no, thank you very much. So this is a first in human Phase I study looking at a novel T-cell engager AZD0486. Now this is a CD19xCD3 antibody, so it’s a different target than the currently available T-cell engagers that target mainly CD20, this targets CD19. The molecule was designed so that the CD3 binding portion of the antibody has low binding affinity. So it’s designed to have a low, potentially for low CRS, cytokine release syndrome. 

Now, this study is a Phase I study. It included a lot of different B-cell non-Hodgkin lymphomas. The data that I presented was mostly the patients with diffuse large B-cell lymphoma. These are patients who have previously failed two previous lines of therapy. Some of them had failed CAR T-cell therapy, bispecific antibodies as well. As a matter of fact, 59% of patients had previously received or previously failed CAR T-cell therapy. 

So again, this is a Phase I escalation study, so there were different dose levels, and we could see that with increasing different doses, we’re seeing somewhat higher responses, and the dose escalation is still ongoing. As of right now, at the 15 milligram target dose, the CR rate has been 39%, which is similar actually between the patients who previously failed CAR-T-cell therapy versus not. So 33 patients had previously failed CAR T-cell therapy, the CR rate so far at this dose was 40%. Similarly with T-cell naive. 

In terms of safety, so CRS mostly occurred during cycle one. They were all grade one. Some patients experienced ICANS as well, neurotoxicity, and those were also during the step-up dosing, and they were reversible. Mostly they resolved some of them within a few hours, some of them within a day, and they had to do with some transient confusion, there were no seizures. 

So currently this study is still ongoing. We’re seeing MRD negativity in 92% in patients who achieved a CR. Again, the latest iteration of the dosing schema is the double step-up dosing, which patients basically get increasing doses during the step-up phase. So basically, they get a priming dose at cycle one, day one, and day eight, and then the target dose is done at day 15. Afterwards, it’s administered every two weeks. And if patients achieve CR on two consecutive scans after cycle six, then they could switch to a monthly schema. So we’re very excited about this new antibody. And the dose escalation is still ongoing. We also presented data during this ASH with the follicular lymphoma data, and we’re very excited about this.

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