EBMT 2024 | EUPLAGIA-1: Phase I trial of GLPG5201, a CD19 CAR-T product, in R/R CLL and Richter’s transformation

The EUPLAGIA-1 study is a Phase I study run by Galapagos, about the development of a new drug to treat patients with relapse/refractory CLL and also patients with Richter’s transformation. So, again, CLL is a quite indolent disease, but once it is a relapsed or refractory to both targeted therapies like BTKIs or BCL inhibitors, they start, behaving, you know, in quite an aggressive way. The same thing happens to patients with Richter’s transformation. There is no clear standard of care to these patients because even upfront chemoimmunotherapy achieves very low response rates, and it always depends on the performance of a subsequent allogeneic stem cell transplant. So in this setting, we need to develop CAR T-cell therapies to try to be a response, an answer to these patients with unmet need.

So the EUPLAGIA-1 trial is a study that focuses on these patients, must have been relapsed or refractory to at least two or more lines, except for Richter’s transformation patients that could receive CAR T-cells upfront. So this study has a couple of special things. One of it is autologous therapy. But, the CAR T-cells are manufactured fresh in fresh out. So the patient performs apheresis and right away starts the lymphoid depletion chemotherapy and then receives CAR T-cells. So all patients receive the CAR T-cells, all the enrolled patients receive it in a median of just seven days, which allows for CAR T-cell therapy without the need of bridging therapy. And, of course, cutting down times, turnaround times to almost like an off-the-shelf therapy without being an off-the-shelf therapy.

So in the end, these patients, we have treated 15 patients. We haven’t seen any new safety signal, and we have seen an incidence of CRS of around 50%. But most importantly, no case of severe CRS and no case of no grade ICANS. And as for, efficacy, we have seen an overall response rate, an objective overall response rate of more than 90%, and around 60% of complete response rates. And most importantly, these responses seem to be durable. Around, 75% of patients were still in remission at the last data cutoff. So, it seems like GLPG5201, is the name of the CAR, it’s able to achieve deep and durable remissions in these very complex and aggressive disease. So we will be looking forward to starting a Phase II clinical trial with the dose that has been selected of 1 million CAR-T cells per kilo in a multinational trial to be started maybe next year.