ASH 2025 | Investigating AZD0120, a dual-targeting CAR-T product, in R/R myeloma: DURGA-1 preliminary results

Yeah, I’m excited to present the early results, the preliminary results of the Phase Ib DURGA-1 study. This is a safety and efficacy analysis of patients who have had at least three prior lines of therapy and are triple-class exposed, so a notoriously difficult group of patients to treat. This is a novel CAR-T product that targets two antigens, BCMA and CD19. BCMA is universally expressed on the majority of malignant plasma cells. CD19, on the other hand, is widely expressed on various phases of B-cell development and on some subsets of myeloma cells and progenitor cells. Also, in addition, this particular product has a different manufacturing platform. While traditional manufacturing takes several weeks for the CAR T-cells to be made, this particular one is on a FasTCAR platform that manufactures CAR T-cells in less than three days, making it potentially available to more patients who need the CAR-T. 

In addition, because the ex vivo manufacturing is eliminated, so these cells just go through activation and transduction and the expansion is completely in vivo, so the CAR T-cells that are made are younger and fitter and more naive, and so only a small cell dose is required and that improves the safety. So in fact, when we looked at the safety data, the majority of adverse events were hematological. While 80% had neutropenia, this was short term. The thrombocytopenia and anemia were much less. There were no deaths or dose-limiting toxicities, and infections were very low. Less than 10% had grade 3 infections on the study. In terms of CRS and ICANS, the CRS rate was only 62%, only 46% required tocilizumab. And of the 16 patients on this 26 patient study, 15 of them had grade 1 CRS. So there was only one grade 2 CRS. In terms of ICANS, there was only one grade 1 ICANS event reported in the entire study. There were no delayed toxicities, no delayed neurotoxicities, no Parkinson’s disease or Guillain-Barré. There was no cranial nerve palsies. There was no IEC-associated colitis. So really a very well-tolerated CAR-T product. And in fact, a third of the patients received the CAR-T infusion as an outpatient. 

So in terms of the efficacy, the short follow-up, the median follow-up is 3.9 months, but 96% was the response rate, 78% were CR or better, 17% were partial response, and in the MRD evaluable population, 94% were MRD negative, and all of this happened in the first month. So we are very excited to look ahead to more updates on this study, both in terms of toxicity and particularly in terms of efficacy, I think this is something to follow.

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