Clinical Summary:

• Design/Population: Arm B of the phase 1b MONVISO study evaluated etentamig, a next-generation BCMA×CD3 bispecific T-cell engager, in heavily pretreated patients with relapsed or refractory multiple myeloma previously exposed to BCMA-directed therapy, including CAR T-cell therapy or antibody-drug conjugates. 
• Key Outcomes: Etentamig demonstrated meaningful and durable activity despite prior BCMA exposure, with the strongest responses observed in patients who received BCMA CAR T-cell therapy as their most recent treatment. Responses were deep, including MRD negativity in evaluable patients, and remained durable with clinically meaningful progression-free survival.
• Clinical Relevance: These findings suggest that etentamig may provide an effective treatment option following prior BCMA-directed therapy and support its development as a next-generation bispecific antibody with the potential for simplified monthly dosing and improved outpatient administration.

Saurabh Chhabra, MD, Mayo Clinic, Phoenix, Arizona, discusses results from the phase 1b MONVISO study evaluating etentamig in patients with relapsed or refractory multiple myeloma previously treated with BCMA-targeted therapies. As BCMA-directed therapies move earlier in the treatment paradigm, identifying effective sequential treatment strategies has become an increasingly important clinical challenge.

Etentamig produced durable responses in a heavily pretreated population, including patients whose disease had previously been exposed to CAR T-cell therapy or antibody-drug conjugates targeting BCMA. The study also demonstrated a favorable safety profile, with predominantly low-grade cytokine release syndrome despite administration without step-up dosing, supporting the potential for a more convenient monthly dosing strategy and broader outpatient use.

Dr Chhabra presented these results at the European Hematological Association (EHA) Annual Meeting in Stockholm, Sweden. 

Transcript: 

Hi, my name is Saurabh Chhabra, I am a hematologist-oncologist and a transplant and cell therapy physician at Mayo Clinic Arizona. I am also the associate director of the blood and marrow transplant program and section head of the myeloma program at Mayo Clinic Arizona.

I'm honored to present the results of the MONVISO study, specifically Arm B and Arm C, on behalf of my coinvestigators. This is a phase Ib clinical trial that investigated the use of a BCMA bispecific antibody called etentamig in triple-class exposed relapsed or refractory multiple myeloma patients. Arm B of the MONVISO trial specifically investigated the use of etentamig in prior BCMA-exposed relapsed or refractory multiple myeloma patients. 

Etentamig is a BCMA bispecific antibody that is made up of a low-affinity CD3-binding domain and a bivalent high-affinityBCMA-binding domain. It has a silenced Fc, which allows an extended half-life and enables convenient 4-weekly dosing. There are data from the first-in-human phase 1 trial of etentamig that showed an overall response rate of 66% in a heavily pretreated relapsed or refractory patient population and a cytokine release syndrome rate of approximately 30% without the implementation of a step-up dose.

Now, in the MONVISO trial, the overarching goal was to define an optimal etentamig dosing schedule through further reduction in the risk of cytokine release syndrome so as to enable safe upfront outpatient administration. Arm A evaluated etentamig in triple-class exposed relapsed or refractory myeloma patients who had no prior BCMA therapy exposure. Arm B evaluated etentamig in triple-class exposed relapsed or refractory myeloma patients with prior BCMA exposure, but without any step-up dosing. Arms C and D evaluated etentamig in the outpatient setting. Arm D specifically is looking at the use of etentamig in community oncology practices.

Starting with Arm B, as I mentioned, triple-class exposed relapsed or refractory myeloma patients who had prior BCMA therapy exposure, which could have been in the form of prior BCMA CAR T-cell therapy or a prior BCMA antibody-drug conjugate, were eligible for this cohort. Prior BCMA bispecific antibody or T-cell engager therapy was an exclusion. Patients were treated with a dose of 60 mg once monthly without any step-up dosing. The primary end point was safety, and preliminary efficacy was also evaluated. 

In this cohort, 41 patients were treated with etentamig, including 24 patients who had received prior BCMA CAR T-cell therapy and 17 patients who had received a prior BCMA antibody-drug conjugate. This was a heavily pretreated patient population with a median of 6 prior lines of therapy. Approximately half the patients had received BCMA-directed therapy as their last line of therapy. The median time from the last dose of the previous BCMA-directed therapy to the first dose of etentamig was approximately 16 months in the patients who received prior BCMA CAR T-cell therapy and approximately 4 months in patients who received a prior BCMA antibody-drug conjugate. Approximately 40% of the patients did not respond to their previous BCMA-directed therapy, including 25% of patients who had received prior BCMA CAR T-cell therapy, and this reflects the difficult-to-treat nature of this patient population. 

Looking at the efficacy data, after a median follow-up of approximately 14 months, the data showed deep responses with etentamig in approximately 50% of the patients. Looking specifically at the efficacy in patients who received a prior BCMA antibody-drug conjugate, the overall response rate was approximately 50% as well. However, in patients who received BCMA CAR T-cell therapy as the immediate prior line of therapy before receiving etentamig, the overall response rate was 64%, with all responses being very good partial response or deeper. 

The deep responses obtained with etentamig were also durable.  With a median follow-up of 14 months, the duration of response in patients who received prior BCMA CAR T-cell therapy as the immediate prior line was approximately 13 months. Progression-free survival was also clinically meaningful, with a median of approximately 12.7 months. 

Looking at the safety data, approximately 70% of patients ended up discontinuing treatment, mostly because of disease progression. The majority of adverse events could be managed without the need for treatment discontinuation. Infectious adverse events led to treatment discontinuation in 1 patient and death in 2 patients. No patients discontinued treatment or died as a result of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome (ICANS). The remaining adverse event profile was consistent with previous data, with no new safety signals observed. 

I would also like to mention the safety data from Arm C of the MONVISO study. Again, the objective of Arm C was to define the optimal etentamig dosing schedule in the outpatient treatment setting. In this cohort, approximately 60 patients who were triple-class exposed and may have had prior BCMA exposure were treated with a single step-up dose of etentamig, 2 mg on cycle 1 day 1, followed by 60 mg of etentamig on cycle 1 day 4, and subsequently every month thereafter.

Interestingly, the incidence of CRS was as high as 57% in Arm B of the MONVISO study, with no high-grade events. Most of the events were actually grade 1, and this was without the implementation of a step-up dose. With the implementation of a step-up dose in Arm A, the rate of CRS was reduced to 30%. In Arm C of the MONVISO study, the CRS rate was approximately 27%. In this cohort, 16 out of 60 patients received prophylactic tocilizumab, which was administered at the investigator's discretion and was not mandated by the protocol. Among those 16 patients, none developed CRS.

This suggests that etentamig dose optimization, which includes implementation of a single step-up dose together with prophylactic tocilizumab, has the potential to eliminate the risk of CRS. This may be the key to overcoming the barrier to the delivery of etentamig and improving its access in the outpatient setting, particularly in community practices.

I also want to mention that outpatient management of etentamig is feasible. Of the 16 patients in Arm C who developed CRS, only 8 required hospitalization. The median time to improvement or resolution of CRS was 5 hours in this cohort. The median age, I should point out, of this cohort was 74 years. It is important to note that no patient developed recurrent CRS, regardless of whether CRS developed after the step-up dose or after the first treatment dose. None of the patients had recurrent CRS.

In summary, despite prior BCMA exposure, etentamig produces deep and durable responses. The outcomes are particularly encouraging in patients who received BCMA CAR T-cell therapy as the immediate prior line of therapy, supporting the use of etentamig in patients progressing after BCMA CAR T-cell therapy.  The optimal dosing strategy of combining prophylactic tocilizumab with a single step-up dose of etentamig has the potential to eliminate the risk of CRS and help improve access to this therapy for patients with myeloma. Lastly, the convenient four-weekly dosing schedule of etentamig with a single step-up dose is now being implemented across all of the clinical trial programs with etentamig. 

Source:

Chhabra S, Searle E, Popat R, et al. Etentamig in patients (pts) with relapsed/refractory multiple myeloma (RRMM) with prior exposure to B-cell maturation antigen (BCMA)-targeted therapy. Presented at EHA Congress. June 11 - June 14, 2026. Stockholm, Sweden. Abstract EHA-2799.