Etentamig Shows Superior Efficacy vs SOC in Relapsed/Refractory Myeloma

Etentamig, a BCMA/CD3 bispecific antibody, significantly improved objective response rate (ORR) and progression-free survival (PFS) vs investigator’s choice of standard available therapies (SAT) in patients with triple-class exposed relapsed/refractory multiple myeloma, meeting both co-primary end points of the phase 3 CERVINO trial (NCT06158841) presented at the 23rd Annual International Myeloma Society (IMS) Meeting & Exposition.¹

What were the response and progression-free survival outcomes?

At a median follow-up of 11.4 months (range, 0.5-24.3) among 393 randomly assigned patients, etentamig met the first co-primary end point, producing an ORR of 74.0% vs 45.7% with SAT, a difference of 28.3% (95% CI, 18.5%-37.5%; P <.0001). Responses were deeper with etentamig, with a very good partial response or better in 63% vs 20% of patients and a complete response (CR) or better in 40% vs 7%. Among patients who achieved a CR or better, rates of measurable residual disease (MRD) negativity were considerably higher with etentamig than SAT at both the 10⁻⁵ and 10⁻⁶ thresholds.

Etentamig also met the second co-primary end point of PFS, with the median PFS not reached (NR) vs 6.2 months with SAT (HR, 0.40; 95% CI, 0.29-0.54; P <.0001). The 12-month PFS rates were 62.1% vs 28.4%. The PFS benefit was observed across all prespecified subgroups, including by age, cytogenetic risk, number of prior lines of therapy, and drug-class refractory status. The median duration of response (DOR) was NR with etentamig vs 10.2 months with SAT, and the 12-month DOR rate was 79.6% vs 48.1%.

What was the overall survival signal?

In an analysis of the key secondary end point of overall survival (OS), etentamig reduced the risk of death from any cause by 52% (HR, 0.48; 95% CI, 0.29-0.77; P = .0012), although the prespecified efficacy boundary for OS was not crossed at the data cutoff. The 12-month OS rate was 87.9% with etentamig vs 72.0% with SAT, and the median OS was NR in either arm.

The non-relapse mortality rate was 5.1% with etentamig vs 9.8% with SAT, and infection-related non-relapse mortality occurred in 1.5% vs 3.1%. Among patients in the SAT arm who received post-study therapy, 75% went on to receive a T-cell–redirecting therapy, such as a bispecific antibody or CAR T-cell therapy.

What was the safety profile of etentamig?

Etentamig was administered with a single step-up dose (SUD) implemented during the study based on phase 1 dose-optimization data. Among the 113 patients treated with the single SUD, cytokine release syndrome (CRS) occurred in 28.3% of patients and was predominantly grade 1, with grade 2 events in 4.4% and no grade 3 or higher events. Across all etentamig-treated patients before the single SUD was implemented, the CRS rate was 39.5%.

Among 22 patients who received prophylactic tocilizumab (Actemra) with the single SUD, no CRS occurred. A single grade 1 case of immune effector cell–associated neurotoxicity syndrome (ICANS) was reported. Grade 3/4 infections occurred in 27.7% of etentamig-treated patients vs 19.2% with SAT, grade 5 infections occurred in 1.5% vs 3.1%, and any-grade opportunistic infections occurred in 3.6% vs 1.6%. Adverse events led to treatment discontinuation in 3.6% of the etentamig arm vs 14.0% of the SAT arm.

“CERVINO met both primary end points in a diverse and heavily pretreated population reflective of real-world clinical practice. Etentamig improved ORR, depth of response, and DOR. Etentamig reduced the risk of disease progression or death by 60% vs standard of care and across all subtypes,” lead study investigator Peter Voorhees, MD, chief of the Plasma Cell Disorders Division at Atrium Health Levine Cancer Institute, stated in his presentation of the data.¹ “[I]t’s safe to argue that CERVINO establishes etentamig as a [much] safer BCMA bispecific antibody with a CRS signal and an ICANS signal that’s never been seen before.”

What is the CERVINO design, and what distinguishes etentamig?

CERVINO is a registrational phase 3 trial that enrolled 393 patients with relapsed/refractory multiple myeloma who had received at least 2 prior lines of therapy; were triple-class exposed to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 monoclonal antibody; and had no prior BCMA exposure.² Patients were randomly assigned 1:1 to etentamig (n = 196) or investigator’s choice of SAT, which included carfilzomib (Kyprolis) plus dexamethasone, selinexor (Xpovio) plus bortezomib (Velcade) and dexamethasone, or elotuzumab (Empliciti) plus pomalidomide (Pomalyst) and dexamethasone (n = 197). Etentamig was given at 60 mg every 4 weeks following the single SUD, with outpatient initiation allowed, and treatment discontinuation permitted after a minimum of 24 cycles in patients with a sustained CR or better for at least 12 months.

The trial’s primary end points were ORR and PFS. Secondary end points included OS, the CR rate or better, very good partial response rate or better, MRD negativity, and patient-reported outcomes.

Etentamig is a second-generation BCMA/CD3 bispecific antibody with a bivalent, high-avidity BCMA-binding domain and a low-affinity CD3-binding domain designed to mitigate CRS and infection risk while preserving T-cell fitness. In a subgroup treated at non-academic centers (n = 53, approximately 27% of the etentamig arm), grade 3/4 infections occurred in 22.6% of patients, and CRS occurred in 23.3% with no grade 3 or higher events, which the investigators said supports the feasibility and safety of etentamig in non-academic and outpatient settings.

References

1. Voorhees P, Mateos MV, Costa L, et al. CERVINO: phase 3 results of etentamig vs investigator’s choice of standard available therapies in patients with triple-class exposed relapsed or refractory multiple myeloma (RRMM). Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland. Abstract LBA-01.
2. Study assessing activity of intravenous (IV) etentamig monotherapy versus standard available therapies in adult participants with relapsed or refractory multiple myeloma (CERVINO). ClinicalTrials.gov. Updated August 27, 2026. Accessed September 26, 2026. https://tinyurl.com/ym3c7kbe