EHA 2026 | Phase I study of etentamig in R/R AL amyloidosis: safety & efficacy data

So in this meeting, we will present the data about etentamig, which is a new bispecific BCMA CD3 targeting antibody, which is engineered to have a bivalent BCMA binding domain, but also a CD3 binding domain that has lower affinity, and which is engineered to reduce the incidence of CRS. Also, it has an FC tail, which allows the drug to be given every four weeks. So since BCMA is expressed on the plasma cells that produce the amyloidogenic light chains, and etentamig could be a very promising therapy for patients with AL amyloidosis. In ASH meeting a few months ago, the initial phase one dose escalation study results were presented and showed that this was a very effective and very safe drug when given as a monotherapy. According to these results, the 40 milligram dose given every four weeks will be promoted for the Phase II dosing of the study. In this meeting, we present updated data regarding the safety and the efficacy in the three-dosing cohorts of 20, 40, and 60 milligram. Patients with relapsed or refractory AL amyloidosis were included, stage 1, 2, or 3A, who had been exposed to daratumumab or other ADC-CD38 monoclonal antibody and proteasome inhibitor. And also, all the patients had measurable disease defined as a dFLC above 50. Three dosing cohorts were evaluated 20 milligram and 40 and 60 milligram every four weeks. In the 40 and 60 milligram there was also a step-up dosing of two milligrams given on day one and the full dose of 40 or 60 milligrams on day four on the first cycle and subsequently in each cycle on the first day the full dose of 40 or 60 milligrams on day four of the first cycle. And subsequently, in each cycle, on the first day, the full dose of 40 or 60 milligrams was given with premedication that included also dexamethasone, paracetamol, and antihistamines. So in this analysis, there were no new dose-limiting toxicities after a median follow-up of about 10 months. More than 90% of the patients continued to receive treatment with etentamig. The CRS prevalence was very low. It was just three patients, all of which had a single episode of CRS, in all of which it was grade one. There was no ICANS and there was no recurrence of the CRS. Another important finding was that the incidence of infections was very low. There were just two patients who had grade 3 infections. There were no grade 4 infections, no patients discontinuing therapy for infections. The efficacy was also impressive, and in the updated follow-up, the complete hematologic response rate was 100% across all the dosing levels. Specifically for the dosing level of 40 milligrams, which is evaluated in the Phase II portion of the study, it was 100% complete hematologic response rates. Among the evaluable patients, 8 out of 8 were also MRD negative, and the median time to complete hematologic response rate was just one month. Also, the time to reduction of the involved free light chain to levels below 10 milligrams per liter was just seven days, just one week. And this was also associated with very high levels of organ responses, which were also rapid, including cardiac responses in the evaluable patients and also renal responses. So taking all this together, etentamig seems to be a very promising, very effective, very safe therapy for patients with relapsed AL amyloidosis. And based on these results, and the results of the Phase II study that is ongoing, has fully enrolled, it is expected that a Phase III registrational study evaluating etentamig against daratumumab VCD will start in patients with newly diagnosed AL amyloidosis.

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