BLA Submitted for Etentamig in Relapsed/Refractory Myeloma

A biologics license application (BLA) has been submitted to the FDA for etentamig (ABBV-383), an investigational BCMA x CD3 bispecific T-cell engager, for adults with relapsed/refractory multiple myeloma (RRMM).¹

The application is based on the phase 3 CERVINO trial (NCT06158841), in which etentamig resulted an overall response rate (ORR) of 74.0% vs 45.7% with investigator's choice of standard available therapies (SAT) and reduced the risk of disease progression or death by 60% (HR, 0.40; 95% CI, 0.29-0.54; P < .0001) in patients with triple-class–exposed disease.² Etentamig also displayed a favorable safety profile after a single step-up dose and every-4-weeks administration. The results were presented at the 2026 International Myeloma Society (IMS) Annual Meeting by Peter Voorhees, MD.

“Adoption of these incredibly effective therapeutics has been suboptimal, and that’s not good for patients,” Voorhees, professor of cancer medicine at Atrium Health Levine Cancer Institute, said in an interview with Targeted Oncology^TM. “We’re hopeful that this will be a game changer and increase the comfort level of using these [agents] in the community setting.”

CERVINO Trial Design

The global, open-label CERVINO study randomly assigned 393 patients 1:1 to intravenous etentamig or SAT. Eligible patients had received at least 2 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. SAT options were carfilzomib (Kyprolis) plus dexamethasone; elotuzumab (Empliciti) plus pomalidomide (Pomalyst) and dexamethasone; or selinexor (Xpovio) plus bortezomib (Velcade) and dexamethasone.¹

ORR and progression-free survival (PFS) were the dual primary end points. Key secondary end points include overall survival (OS), depth of response, measurable residual disease negativity, disease symptoms, and physical functioning.

Efficacy Findings

AbbVie first announced topline results from CERVINO in September 2026. Patients had received a median of 3 prior lines of therapy, and median follow-up was 11.4 months. The ORR was 74.0% (95% CI, 67.25%-79.97%) with etentamig and 45.7% (95% CI, 38.59%-52.91%) with SAT (P < .0001).

At IMS, Voorhees reported that median PFS had not been reached in the etentamig arm vs 6.2 months in the SAT arm. The 12-month OS rate was 87.9% with etentamig and 72.0% with SAT (HR, 0.48; 95% CI, 0.29-0.77; nominal P =.0012), although the prespecified efficacy boundary for OS had not yet been crossed.

Safety Findings

The most common treatment-emergent adverse events (TEAEs), occurring in at least 25% of patients receiving etentamig, were cytokine release syndrome (CRS), hypogammaglobulinemia, neutropenia, and anemia. TEAEs led to discontinuation in 3.6% of patients in the etentamig arm and 14% of those in the SAT arm, according to the BLA announcement.

Among patients who received the single step-up dose, CRS occurred in 28.3% and was limited to grade 1 (23.9%) or grade 2 (4.4%) events; 1 patient had grade 1 immune effector cell–associated neurotoxicity syndrome (ICANS). Voorhees highlighted this as a key feature of this bispecific antibody compared with existing drugs of this class. Across all etentamig-treated patients, the CRS rate was 39.5% and the ICANS rate was 3.6%.

Grade 3 or 4 infections were more frequent with etentamig than with SAT (27.7% vs 19.2%), but grade 5 infections were less frequent (1.5% vs 3.1%). Fatal TEAEs of any cause occurred in 2.6% and 5.7% of patients, respectively.

Design and Rationale

Etentamig pairs a low-affinity CD3-binding domain, intended to limit CRS and infections, with a high-affinity bivalent BCMA-binding domain. Retained neonatal Fc receptor binding supports dosing every 4 weeks, according to AbbVie. The company noted in its news release that the link between these structural features and clinical effects is still under investigation.

The company emphasized the potential of etentamig as a treatment that could be delivered in community settings, citing the CRS, infection, neurotoxicity, and monitoring requirements that it says limit broader use of existing BCMA-directed bispecific antibodies and chimeric antigen receptor T-cell therapies.

REFERENCES

1. AbbVie submits biologics license application (BLA) for etentamig to U.S. FDA for adults living with relapsed/refractory multiple myeloma. News release. AbbVie. October 27, 2026. Accessed October 27, 2026. https://tinyurl.com/4t7hdc2x

2. Voorhees P, Mateos MV, Costa L, et al. CERVINO: phase (Ph) 3 results of etentamig vs investigator's choice of standard available therapies (SAT) in patients (pts) with triple-class exposed relapsed or refractory multiple myeloma (RRMM). Presented at: 23rd IMS Annual Meeting & Exposition; September 23-26, 2026; Glasgow, Scotland. LBA-01.