AbbVie has submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for etentamig, an investigational BCMA × CD3 bispecific antibody, for adults with relapsed or refractory multiple myeloma.
The regulatory submission is supported by results from the Phase 3 CERVINO trial, in which etentamig significantly improved both overall response rate (ORR) and progression-free survival (PFS) compared with investigator-selected standard available therapies in patients with heavily pretreated, triple-class exposed multiple myeloma.
Etentamig, previously known as ABBV-383, is administered intravenously and uses a single step-up dose followed by once-every-four-weeks dosing from treatment initiation, an approach AbbVie is positioning as potentially compatible with a broader range of treatment settings, including outpatient and community-based care.
Phase 3 CERVINO Trial Supports the FDA Submission
The global, randomized, open-label Phase 3 CERVINO trial (NCT06158841) enrolled 393 patients with relapsed or refractory multiple myeloma who had received at least two previous lines of therapy.
All patients had previously been exposed to the three major treatment classes used in multiple myeloma: a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 monoclonal antibody. Patients had received a median of three previous lines of therapy.
Participants were randomized 1:1 to receive etentamig or the investigator’s choice of standard available therapy, which included:
- carfilzomib plus dexamethasone;
- elotuzumab plus pomalidomide and dexamethasone; or
- selinexor plus bortezomib and dexamethasone.
The trial’s dual primary endpoints were ORR and PFS.
At a median follow-up of 11.4 months, ORR reached 74.0% with etentamig compared with 45.7% with standard available therapy (P<0.0001).
Etentamig also reduced the risk of disease progression or death by 60%, with a hazard ratio for PFS of 0.40 (95% CI, 0.29–0.54; P<0.0001). Median PFS had not yet been reached in the etentamig arm, compared with 6.2 months in the control group. The PFS benefit was reported across all prespecified subgroups evaluated.
Responses were also deeper with etentamig. At least a complete response was reported in approximately 40% of patients receiving etentamig compared with 7% receiving standard therapy.
An early overall survival signal also favored etentamig. Twelve-month OS was 87.9% versus 72.0%, although the prespecified efficacy boundary for overall survival had not been crossed at the time of the analysis, meaning the OS findings remain immature.
Monthly Dosing and Safety
Beyond efficacy, AbbVie is emphasizing etentamig’s dosing schedule and safety profile as potentially important features of the therapy.
Etentamig incorporates one step-up dose followed by monthly dosing from initiation, rather than requiring more frequent ongoing administration.
Among patients treated using the single step-up dosing strategy, cytokine release syndrome (CRS) occurred in 28.3%. Most events were grade 1 (23.9%), while 4.4% were grade 2. No grade 3 or higher CRS events were reported in this group. One patient experienced grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS).
The most frequently reported treatment-emergent adverse events with etentamig included CRS, hypogammaglobulinemia, neutropenia, and anemia.
Infections remain an important consideration. Grade 3 or 4 infections occurred in 27.7% of patients receiving etentamig compared with 19.2% receiving standard therapy. Grade 5 infections occurred in 1.5% and 3.1% of patients, respectively.
Adverse event-related treatment discontinuation was reported in 3.6% of patients receiving etentamig.
What Is Etentamig?
It is an investigational second-generation BCMA × CD3 bispecific T-cell engager.
The antibody is designed to simultaneously bind B-cell maturation antigen (BCMA), which is highly expressed on malignant plasma cells, and CD3 on T cells, bringing the immune cells into proximity with myeloma cells and promoting T-cell-mediated killing.
Its structure includes a high-affinity bivalent BCMA-binding domain and a lower-affinity CD3-binding domain. According to AbbVie, the latter was designed with the aim of reducing inflammatory toxicities such as CRS, while retained FcRn binding supports the drug’s once-every-four-weeks dosing schedule. The relationship between these structural characteristics and observed clinical outcomes continues to be investigated.
BCMA has already emerged as a major therapeutic target in multiple myeloma through both bispecific antibodies and CAR T-cell therapies. However, requirements for step-up dosing, monitoring, management of CRS and neurotoxicity, and infection risk can complicate delivery, particularly outside specialized treatment centers.
Etentamig’s clinical development is therefore exploring whether BCMA-directed T-cell engagement can be combined with a less intensive dosing schedule that may facilitate treatment in a wider range of clinical settings.
Daejin Abidoye, MD, Vice President and Therapeutic Area Head, Oncology, Solid Tumor and Hematology at AbbVie, said:
“Patients deserve therapeutic options that are not only effective, but also support the realities of when, where and how they receive treatment.”
What Comes Next for Etentamig?
The October 27 submission moves etentamig into U.S. regulatory review territory, but the drug remains investigational and is not currently FDA-approved. AbbVie has not yet announced an FDA acceptance of the BLA or a Prescription Drug User Fee Act (PDUFA) action date.
The company is meanwhile expanding the development program for etentamig into additional multiple myeloma settings and combinations. Clinical studies are evaluating the agent across different stages of the disease, including earlier-line and newly diagnosed multiple myeloma.
If ultimately approved, etentamig would add another BCMA-directed option to an increasingly competitive multiple myeloma treatment landscape. The CERVINO findings suggest that its potential differentiation may depend not only on response and disease control, but also on whether its monthly dosing strategy can translate into more practical use across both academic and community oncology settings.
Read further on OncoDaily: Etentamig and the Next Wave of Immune Engagers in Multiple Myeloma
