ASH 2024 | A Phase I trial of trispecific CAR T-cells targeting CD19/20/22 in B-cell malignancies

So this is our Phase I clinical trial with point of care manufacturer of this autologous trispecific CAR T-cells against CD19, 20 and CD22 for relapsed/refractory B-cell malignancies. So on this trial we’re able to have in-house manufacturing of our CAR T-cell products, what allows us the patients to be leukapheresed on day minus seven and start lymphodepletion the day after, day minus six, with a vein-to-vein time of seven to nine days. And we had a 94% successful manufacture and allow a high ratio of infusion enrollment in the trial, which is a frequent limitation in CAR-T trials because of the prolonged time for manufacture. Some patients are not able to receive the CAR Tpcells since the collection through the infusion. In this trial we include diverse patients with relapsed/refractory B-cell malignancies like B-cell non-Hodgkin lymphoma, B-cell ALL, CLL including Richter’s. We treated 15 patients, it was a heavily treated patient population, the median line of therapy was three, 47% have bulk disease. And despite these aggressive features of this patient population, like I said, we were able to infuse 94% of the patients with CAR T-cell products in a short vein-to-vein time. We did not see any safety concerns, we did not have any dose-limiting toxicities, no cases of high-grade CRS, no cases of ICANS, HLA, and most of the delayed hematologic recovery associated with the disease. We did see a signal of efficacy in B-cell non-Hodgkin lymphoma. Among the six patients with B-cell non-Hodgkin lymphoma, we have an 83% CR rate. Four of the five respondents have durable remission, and we have a median duration of remission of 13 months. In the other disease subgroups, we saw limited efficacy, and we’re still trying to understand what the reason for the limited efficacy in B-cell ALL and CLL. One of the explanations are correlative data. We saw nice expansion of the CAR T-cells in vivo, but not as much persistence beyond day 100. This could be related to our co-stimulatory domain, our vector that is OX40. So in our next steps we might try to use a different co-stimulatory domain.

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