Etentamig Improves Response, Survival in Phase 3 Trial for Relapsed/Refractory Myeloma

Etentamig (ABBV-383), an investigational BCMA x CD3 bispecific T-cell engager, significantly improved objective response rate (ORR) and progression-free survival (PFS) compared with investigator’s choice of standard available therapies in patients with triple-class–exposed relapsed/refractory multiple myeloma (RRMM), according to topline results from the phase 3 CERVINO trial (NCT06158841).¹

Findings from CERVINO, a global, phase 3, multicenter, randomized, open-label trial, showed an ORR of 74.0% (95% CI, 67.25%-79.97%) with etentamig vs 45.7% (95% CI, 38.59%-52.91%) with standard available therapies (P <.0001), along with a 60% reduction in the risk of disease progression or death (HR, 0.40; 95% CI, 0.29-0.54; P < .0001).

"In this heavily pretreated, 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 cytokine release syndrome [CRS],” said Peter Voorhees, MD, chief of the Plasma Cell Disorders Division at Atrium Health Levine Cancer Institute and an investigator on the CERVINO trial, in a news release. “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.”

Drug Background and Trial Design

In a first-in-human phase 1b dose escalation study (NCT05650632), etentamig was well tolerated and resulted in an ORR of 68% at doses of at least 40 mg.²

CERVINO randomly assigned patients with RRMM who had received at least 2 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody, 1:1 to etentamig or standard available therapy. The comparator regimens included carfilzomib (Kyprolis) plus dexamethasone, elotuzumab (Empliciti) plus pomalidomide (Pomalyst) and dexamethasone, or selinexor (Xpovio) plus bortezomib (Velcade) and dexamethasone.¹

Etentamig was administered using an optimized dosing strategy incorporating a single step-up dose followed by once every 4 weeks (Q4W) dosing from initiation. The dual primary end points were ORR and PFS; key secondary end points included overall survival (OS), depth of response, measurable residual disease (MRD) negativity, disease symptoms, and physical functioning.

At a median follow-up of 11.4 months, the trial had enrolled 393 patients who had received a median of 3 prior lines of therapy. The 12-month OS 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 had not been crossed at the time of data cutoff. The PFS benefit was observed across all evaluated prespecified subgroups.

This was the first planned efficacy interim analysis of CERVINO. Based on the observed benefit, the independent data monitoring committee recommended unblinding the study.

Safety Findings

Grade 3/4 infections occurred in 27.7% of patients receiving etentamig vs 19.2% receiving standard available therapies, whereas grade 5 infections occurred less frequently with etentamig (1.5% vs 3.1%). Among patients who received the single step-up dose, the incidence of CRS was 28.3%, predominantly grade 1 (23.9%), with no grade 3 or higher events reported. One patient (0.9%) experienced immune effector cell-associated neurotoxicity syndrome, graded as grade 1, with no grade 2 or higher events reported. Discontinuations related to treatment-emergent adverse events were lower with etentamig than SAT (3.6% vs 9.6%).

Broader Development Context

Etentamig is designed as a second-generation BCMA x CD3 bispecific antibody, combining a low-affinity CD3 binding domain intended to reduce CRS and infection risk with a high-avidity bivalent BCMA-binding domain and retained neonatal Fc receptor binding intended to enable Q4W dosing after a single step-up dose.

Etentamig is being investigated in combination with other agents in RRMM, including with pomalidomide and dexamethasone in the phase 1b Kilimanjaro study (NCT05259839), which showed tolerability and an ORR of 81% in a heavily pretreated population.³ It also showed a manageable safety profile as monotherapy in a phase 1 trial (NCT06158854) for relapsed/refractory light chain amyloidosis with deep and rapid hematologic responses including 100% rate of very good partial response or better.⁴

Full CERVINO results will be presented by Voorhees in a plenary session at the 23rd International Myeloma Society Annual Meeting on September 25, 2026, in Glasgow, Scotland. AbbVie stated that it plans to discuss the CERVINO results with global regulatory authorities to determine next steps for etentamig.

“The phase 3 CERVINO results support the scientific approach behind etentamig and demonstrate the value of designing therapies that address both the biology of multiple myeloma and the practical needs of patients and providers through a manageable safety profile, a convenient dosing schedule and the potential for treatment in outpatient and community-based care settings,” said Daejin Abidoye, MD, vice president and therapeutic area head, oncology, solid tumor and hematology at AbbVie, in a news release.

REFERENCES

1. 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 3, 2026. https://tinyurl.com/4nefthxt

2. Mian H, Baljevic M, Magen H, et al. A Phase 1b study of step-up dosing with ABBV-383, a B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma. Blood. 2024;144(suppl 1):1985. doi:10.1182/blood-2024-206912

3. Voorhees P, D’Souza A, Quach H, et al. Etentamig plus pomalidomide-dexamethasone combination therapy in relapsed or refractory multiple myeloma: A phase 1b dose-escalation and safety expansion study. Blood. 2025;146(suppl 1):247. doi:10.1182/blood-2025-247

4. Charkraborty R, Kastritis E, Huart A, et al. Phase 1/2 dose escalation and expansion study of etentamig in patients with relapsed or refractory light chain amyloidosis. Blood. 2025;146(suppl 1):692. doi:10.1182/blood-2025-692