ASH 2025 | huCART19-IL18 in patients with CLL/SLL or RT after prior BTK inhibitor and venetoclax exposure

We all know that for patients with CLL/SLL who are progressing or have active disease after BTK inhibitors and venetoclax, that those patients really are sort of unmet need in our practices. And we do have one product that’s currently FDA approved, liso-cel, that is a CAR19, autologous CAR19 product that results in responses, but the complete response rate tends to be low. In the pivotal trial, it was just under 20%. So there’s definitely plenty of room for improvement with CAR19 in CLL/SLL patients. 

And so our trial is trying to improve the outcomes. And so we are using a novel product that we also refer to as huCART19-IL18. It’s a fourth-generation CAR product that targets CD19, but at the same time, it also secretes IL-18, and we think that this actually improves the efficacy. We did publish last year, or this past year, our use of this CAR19, this novel CAR, in non-Hodgkin lymphoma patients, and we do conduct at the same time a trial with CLL/SLL, specifically a cohort for CLL/SLL patients. 

We so far have enrolled 10 patients and have seven patients that are available for both efficacy as well as safety, and actually that also includes one patient with Richter’s transformation which is part of the eligibility. And so what we found so far is that in the initial cohort of four patients treated on the dose level one, there were two cases of grade three neurotoxicity, which which made us follow the protocol and de-escalate to dose level minus one, which is three million cells. And the three patients were treated on the dose level minus one, have not had any actually neurotoxicity. I mean, fortunately, even the patients who were treated on the initial dose, the neurotoxicity was transient and without any long-term effects. 

In terms of efficacy, we do find the data encouraging. We are seeing complete responses. Again, the numbers are very, very small, but the complete response rate is 43%, which again compares favorably to the other data from CAR19. And again, these are patients who’ve already had prior venetoclax and BTK inhibitors. Actually, a couple of the patients had liso-cel as well, including the one patient with complete response. So we feel that this data is substantial enough to continue the trial and to expand this dose level minus one. And we’re also doing plenty of correlative studies in these type of trials. So we do see, for example, that the expansion seems to correlate with the response in the CLL/SLL cohort. But again, there’s many more correlative studies that are still pending.

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