Etentamig Significantly Reduces Risk of Progression or Death in Triple-Class Exposed Relapsed or Refractory Multiple Myeloma

Clinical Summary: 

• Design/Population: This phase 3 trial evaluated etentamig vs investigator’s choice of standard available therapies in patients with relapsed or refractory multiple myeloma who received at least 2 prior lines of therapy and were exposed to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 monoclonal antibody.
• Key Outcomes: Etentamig significantly improved response and progression-free survival compared with standard therapies, reducing the risk of progression or death by 60%. Overall survival favored etentamig but remained interim, while cytokine release syndrome was predominantly low grade.
• Clinical Relevance: The significant response and progression-free survival benefits support etentamig as a potential treatment option, while its single step-up dose and monthly dosing schedule may offer a differentiated approach to BCMA-directed bispecific therapy.

Topline results from the phase 3 CERVINO trial demonstrated that etentamig, an investigational second-generation BCMA x CD3 bispecific T-cell engager, significantly improved response and progression-free survival (PFS) compared with investigator’s choice of standard available therapies in patients with triple-class exposed relapsed or refractory multiple myeloma.

In this open-label trial, 393 patients who had received at least 2 prior lines of therapy and had prior exposure to a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody were randomized 1:1 to receive etentamig once every 4 weeks or investigator’s choice of standard available therapy. Standard therapies included carfilzomib plus dexamethasone, elotuzumab plus pomalidomide and dexamethasone, or selinexor plus bortezomib and dexamethasone. Etentamig was administered with a single step-up dose followed by monthly dosing from treatment initiation.

The dual primary end points were objective response rate (ORR) and PFS. Key secondary end points included overall survival (OS) and safety.

At a median follow-up of 11.4 months, ORR was 74% with etentamig compared with 45.7% with standard available therapies (P < .0001), meeting one of the trial’s dual primary end points.

Etentamig also significantly improved PFS, reducing the risk of disease progression or death by 60% compared with standard available therapies (hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.29 to 0.54; P < .0001). The PFS benefit was observed across all prespecified subgroups evaluated.

At 12 months, OS was 87.9% with etentamig compared with 72% with standard available therapies (HR, 0.48; 95% CI, 0.29 to 0.77; nominal P = .0012). However, the prespecified efficacy boundary for OS was not crossed at the data cutoff, and the survival findings remain interim.

Grade 3/4 infections occurred in 27.7% of patients receiving etentamig and 19.2% receiving standard available therapies. Fatal infections occurred in 1.5% and 3.1% of patients, respectively. Among patients receiving etentamig with a single step-up dose, cytokine release syndrome (CRS) occurred in 28.3% and was predominantly grade 1, with no grade ≥3 events reported. One patient experienced grade 1 immune effector cell–associated neurotoxicity syndrome (ICANS), with no grade ≥2 events reported.

Treatment-emergent adverse events led to discontinuation in 3.6% of patients receiving etentamig compared with 9.6% receiving standard available therapies.

Based on the significant benefit observed at this first planned efficacy interim analysis, the Independent Data Monitoring Committee recommended unblinding the CERVINO trial. Etentamig remains investigational, with full findings planned for presentation at the 2026 International Myeloma Society Annual Meeting and discussion with global regulatory authorities.

“Together, with its administration and dosing schedule, these findings support etentamig's role as a BCMA-targeted bispecific treatment option for multiple myeloma patients, with the potential to provide access across a range of treatment settings beyond specialized treatment centers and into outpatient and community-based settings,” stated Peter Voorhees, MD, Atrium Health Levine Cancer Institute, Charlotte, North Carolina.

Source:

AbbVie. AbbVie announces positive topline results from the phase 3 CERVINO trial showing etentamig significantly improved response rate and progression-free survival in patients with relapsed/refractory multiple myeloma. Published online: September 3, 2026. Accessed on: September 3, 2026. https://news.abbvie.com/2026-09-03-AbbVie-Announces-Positive-Topline-Results-from-the-Phase-3-CERVINO-Trial-Showing-Etentamig-Significantly-Improved-Response-Rate-and-Progression-Free-Survival-in-Patients-with-Relapsed-Refractory-Multiple-Myeloma