CAR-T Meeting 2025 | Results of the pivotal CART19-BE-02 trial, a multicenter trial of var-cel for adult R/R B-ALL

So the CART19-BE-02 trial is a pivotal multicenter trial investigating the safety and efficacy of varnimcabtagene autoleucel or var-cel in adult patients with relapsed refractory B-ALL. So this is our first multicenter trial, which is fully academic and has been carried out in eight academic centers across Spain. 

So, this trial was designed to test the efficacy of var-cel in a higher dose as compared to the Phase I/II clinical trial. So in the Phase I/II clinical trial, we treated the patients with a 1 million CAR T-cell dose per kilogram and this was the dose that was selected to be approved as a hospital exemption in Spain for adult patients with B-ALL. So in this trial, what we are trying to do is we are testing a higher dose, so we are giving 3 million CAR T-cells per kilogram as a target dose. So the idea was to see if increasing the dose in these patients was safe and if it could potentially also increase efficacy. 

So what we did, we treated 32 patients with var-cel or varnimcabtagene autoleucel who received at least one dose of varnimcabtagene autoleucel and 23 patients were able to receive the full target dose. So the way that we administer CAR T-cells in this trial is an interpatient dose escalation. So the patient will receive a target dose of 3 million CAR T-cells split into four fractions. So a patient will receive 0.1, 0.3, 0.6 and 2 million CAR-T cells per kilogram separated by at least 24 hours. So depending on how the patient reacts to each dose regarding cytokine release syndrome (CRS), ICANS, fever or infections, a patient could receive one dose or the full four doses. 

So in this trial we were able to treat 32 patients and what we saw is that it was a selection of course patients with high tumor burden and had a median of 41 ages of enrolled patients and had a median of three prior treatment lines. So they have prior being exposed to inotuzumab in 47% of cases and allogeneic stem cell transplant in 66% of cases. And as for tumor load, all patients had measurable disease, up to 86% had leukemic expression in the blood and up to 37% of patients had more than 50% bone marrow blast involvement. So patients with very active disease. 

So what we saw is that almost 72% of patients were able to receive the full four doses, so the target dose of 3 million CAR T-cells per kilogram, and with the remaining nine patients that did not receive the full target dose because of early onset of CRS. So we observed CRS in 75% of patients being severe in 12%. These were four patients that were very high tumor load, both in bone marrow and peripheral blood. These four patients developed CRS, which required the preclusion of var-cel infusions. 

One of the interesting things is that besides CRS, we only observed one case of ICANS, which sort of confirms these characteristics of var-cel, which is a drug that almost does not produce ICANS at all. 

So besides safety, key safety features, so we observed as for efficacy that in the efficacy cohort, meaning patients that receive at least one var-cel infusion, a complete response rate with undetectable measurable residual disease in 84% of patients, which increased to 95% in patients that were able to receive the full four doses. So this is important because of this the trial met its primary endpoint. So the primary endpoint was complete response with undetectable MRD by next generation flow, which is a very sensitive technique, at day 28. So the trial met its primary endpoint and because of this, the outcomes of of this trial are now being evaluated by the European Medicines Agency because these outcomes will be considered for a centralized marketing authorization. So this is a very important thing for academic CAR T-cell therapy because it will be potentially the first time ever that a fully academic CAR T-cell will apply for this sort of authorization. So the intended indication will be adult patients with relapsed/refractory B-ALL.

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