VJToday

Etentamig demonstrates significantly improved ORR and PFS in R/R multiple myeloma: CERVINO topline results

On September 3, 2026, topline results from the CERVINO trial (NCT06158841) were announced, demonstrating significantly improved efficacy and safety outcomes with etentamig versus standard available therapies (SAT) in triple-class exposed patients with relapsed/refractory (R/R) multiple myeloma.1

In recent years, the treatment landscape for multiple myeloma has evolved substantially with the emergence of novel immunotherapies.2 Notably, the approval of several bispecific antibody T-cell engagers has significantly expanded treatment options for patients with R/R disease.2 However, treatment-related challenges are commonly associated with these therapies, including cytokine release syndrome (CRS), infections and frequent dosing, which can increase treatment burden and strain healthcare resources, limiting accessibility in community settings.1 Therefore, a significant unmet need remains for next-generation agents that maintain anti-myeloma activity while offering a convenient dosing schedule and improved tolerability.2  

Etentamig is a second-generation bispecific antibody T-cell engager targeting B-cell maturation antigen (BCMA) and CD3.1 Its bivalent BCMA-binding domain targets BCMA, which is highly expressed on myeloma cells, while its low-affinity CD3-binding domain engages T-cells, bringing them into close proximity with myeloma cells and triggering T-cell-mediated killing.1 The low-affinity CD3 binding is designed to provide sufficient T-cell engagement while limiting cytokine release, potentially reducing the risk of CRS, a common adverse event associated with bispecific therapies.1 The modified Fc region extends the half-life of etentamig, enabling once-every-4-week administration following step-up dosing.1 These unique features have the potential to provide a convenient and well tolerated therapy option.1

The Phase III CERVINO trial is an ongoing, global, multicenter, randomized, open-label study evaluating etentamig in patients with R/R myeloma who have received three prior lines of therapy, including a proteasome inhibitor, immunomodulatory drug and anti-CD38 monoclonal antibody.1 Patients were randomized 1:1 to receive etentamig, administered as a single step-up dose followed by monthly (Q4W) dosing, or SAT selected by the investigator.1

At data cut off, 393 patients were included in the trial, with a median follow-up of 11.4 months. Etentamig met its dual primary end points, with a significantly higher overall response rate (ORR) than SAT (74.0% versus 45.7%, respectively; p<0.0001) and a 60% reduction in the risk of disease progression or death (HR: 0.40; 95% CI: 0.29–0.54; p<0.0001).1 This progression free survival (PFS) rate benefit was observed across all subgroups. The 12-month overall survival (OS) was also higher with etentamig than SAT (87.9% versus 72.0%, respectively; 95% CI: 0.29–0.77; nominal p=0.0012), although the prespecified OS efficacy boundary was not crossed.1

Furthermore, the optimized dosing regimen of etentamig was associated with a manageable safety profile.1 Patients receiving etentamig experienced more grade 3/4 infections compared with SAT (27.7% versus 19.2%); however, fewer grade 5 infections were observed with etentamig (1.5% versus 3.1% with SAT). A low incidence of CRS (28.3%) and immune effector cell-associated neurotoxicity syndrome (ICANS) (0.9%) was observed, and treatment discontinuation due to treatment-emergent adverse events occurred in fewer patients receiving etentamig than SAT (3.6% versus 9.6%).1

To conclude, these topline findings from the CERVINO trial support etentamig as a promising next-generation BCMA-directed bispecific, with the potential to offer an effective and convenient treatment option with a manageable safety profile for patients with R/R multiple myeloma. This approach may broaden access to care beyond specialist centers, extending treatment options into community-based and outpatient settings.

References

  1. 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. Available here. (Last Accessed 08/09/2026)
  2. Waldschmidt JM, Rasche L, Kortüm KM, et al. Comprehensive Review of Bispecific Antibody Constructs In Multiple Myeloma: Affinities, Dosing Strategies and Future Perspectives. Clin Lymphoma Myeloma Leuk. 2025;25(5):309-315.

Written by Clare Harris

Edited by Natalie Markova