Etentamig, an investigational BCMA/CD3 bispecific T-cell engager, met its dual primary end points of objective response rate (ORR) and progression-free survival (PFS) vs standard available therapies (SAT) in patients with triple-class exposed relapsed/refractory multiple myeloma, according to topline results from the phase 3 CERVINO trial (NCT06158841) announced by AbbVie.1
What efficacy did etentamig show in the CERVINO trial?
Among 393 patients who had received a median of 3 prior lines of therapy, at a median follow-up of 11.4 months, the ORR was 74.0% (95% CI, 67.25%-79.97%) with etentamig vs 45.7% (95% CI, 38.59%-52.91%) with SAT (P <.0001). Etentamig significantly improved PFS, showing a 60% reduction in the risk of disease progression or death (HR, 0.40; 95% CI, 0.29-0.54; P <.0001); the PFS benefit was observed across all prespecified subgroups evaluated.
The 12-month overall survival (OS) rate was 87.9% with etentamig vs 72.0% with SAT (HR, 0.48; 95% CI, 0.29-0.77; nominal P = .0012). The prespecified efficacy boundary for OS was not crossed at the data cutoff. This was the first planned efficacy interim analysis of CERVINO; based on the significant benefit, the independent data monitoring committee recommended unblinding the study.
Full results will be presented in a plenary session at the 23rd International Myeloma Society (IMS) Annual Meeting.
What was the safety profile of etentamig?
Etentamig was administered with a single step-up dose followed by monthly or every-4-week dosing from initiation. Grade 3/4 infections occurred in 27.7% of patients receiving etentamig vs 19.2% receiving SAT, and fewer grade 5 infections occurred with etentamig (1.5%) than with SAT (3.1%). Among those who received a single step-up dose, the incidence of cytokine release syndrome (CRS) was 28.3% and predominantly grade 1 (23.9%), with no grade 3 or higher events reported. One patient experienced immune effector cell-associated neurotoxicity syndrome (0.9%; grade 1), with no grade 2 or higher events reported. Treatment-emergent adverse event–related discontinuations were lower with etentamig than with SAT (3.6% vs 9.6%).
“In this heavily pre-treated, triple-class exposed patient population, etentamig delivered clinically meaningful improvements in [PFS] and response rates, alongside a manageable safety profile characterized by predominantly low-grade [CRS],” said Peter Voorhees, MD, chief of the Plasma Cell Disorders Division at Atrium Health Levine Cancer Institute and an investigator on the CERVINO study, in the news release.1 “Together, with its administration and dosing schedule, these findings support etentamig’s role as a BCMA-targeted bispecific treatment option for [patients with] multiple myeloma, with the potential to provide access across a range of treatment settings beyond specialized treatment centers and into outpatient and community-based settings.”
What is the CERVINO trial design?
CERVINO is a global, phase 3, randomized, open-label study evaluating etentamig vs investigator’s choice of SAT in patients with relapsed/refractory multiple myeloma who received at least 2 prior lines of therapy, including exposure to a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. Patients were randomly assigned 1:1 to receive etentamig once every 4 weeks or SAT, which included carfilzomib (Kyprolis) plus dexamethasone, elotuzumab (Empliciti) plus pomalidomide (Pomalyst) and dexamethasone, or selinexor (Xpovio) plus bortezomib (Velcade) and dexamethasone.
The dual primary end points were ORR and PFS. Key secondary end points included OS, depth of response, measurable residual disease negativity, disease symptoms, and physical functioning.
What is etentamig, and what are the next steps?
Etentamig is an investigational, second-generation BCMA/CD3 bispecific antibody T-cell engager composed of a low-affinity CD3-binding domain designed to reduce CRS and infections, a high-avidity bivalent BCMA-binding domain, and retained FcRn binding to enable dosing once every 4 weeks after a single step-up dose. Developers stated that the dosing schedule and clinical profile may support use across a range of settings, including outpatient and community-based care.
Previously, etentamig produced durable responses and was well tolerated in patients with relapsed/refractory multiple myeloma in a first-in-human phase 1 trial (NCT03933735) and phase 1b study (NCT05650632) based on data presented at the European Hematology Association 2025 Congress.² Developers plan to discuss the CERVINO results with global regulatory authorities to determine next steps; etentamig is not approved by any regulatory authority.
References
- 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. News release. AbbVie. September 3, 2026. Accessed September 4, 2026. https://tinyurl.com/mtxtxhps
- Baljevic M, Voorhees P, Rodriguez C, et al. Long-term efficacy and safety of etentamig (ABBV-383), a B-cell maturation antigen (BCMA) bispecific antibody in patients with relapsed/refractory multiple myeloma (RRMM). Abstract presented at: European Hematology Association 2025 Congress; June 12-15, 2025; Milan, Italy. Abstract PF722.
