AbbVie Submits Etentamig BLA After Response and PFS Gains

AbbVie has submitted a biologics license application (BLA) to the US Food and Drug Administration (FDA) for etentamig (ABBV-383), an investigational treatment for adults with relapsed or refractory multiple myeloma (RRMM). The application is supported by the Phase 3 CERVINO trial, which met its dual primary endpoints of overall response rate (ORR) and progression-free survival (PFS) against investigator-selected standard available therapies (SAT).

The results suggest that etentamig could offer an additional treatment option for patients whose disease has progressed after multiple prior therapies. However, its infection profile and the still-immature overall survival findings remain important considerations.

Etentamig and Its Dosing Strategy

Etentamig is an intravenous, second-generation bispecific T-cell engager that targets B-cell maturation antigen (BCMA) on myeloma cells and CD3 on T cells, bringing immune cells into proximity with malignant plasma cells. Its low-affinity CD3-binding domain is designed to reduce cytokine release syndrome (CRS), while its high-affinity, bivalent BCMA-binding domain and retained neonatal Fc receptor (FcRn) binding support the intended dosing strategy.

Unlike regimens requiring frequent administration, etentamig is given after a single step-up dose, followed by dosing every four weeks from treatment initiation. The relationship between these structural features and clinical outcomes remains under investigation.

CERVINO Trial Design and Patient Population

CERVINO (NCT06158841) was a global, randomized, open-label Phase 3 study involving 393 patients with triple-class-exposed RRMM. Participants had received at least two previous lines of therapy, including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 monoclonal antibody.

Patients were randomized 1:1 to receive etentamig or investigator-selected SAT. Comparator regimens included carfilzomib plus dexamethasone, elotuzumab plus pomalidomide and dexamethasone, or selinexor plus bortezomib and dexamethasone.

At the reported analysis, patients had received a median of three prior lines of therapy, reflecting a heavily pretreated population with limited treatment options. The open-label design and investigator-selected comparator are relevant when interpreting the comparative results.

Response Rate and Progression-Free Survival

At a median follow-up of 11.4 months, etentamig achieved an ORR of 74.0%, compared with 45.7% with SAT, an absolute difference of 28.3 percentage points (95% CI, 18.49–37.46; P<0.0001). Complete response or better was reported in 40% versus 7%, while very good partial response or better occurred in 63% versus 20%.

PFS, the time from the trial-defined starting point until disease progression or death, was the second primary endpoint. Median PFS was not reached with etentamig at the analysis cutoff, compared with 6.2 months with SAT. The hazard ratio was 0.40 (95% CI, 0.29–0.54; P<0.0001), corresponding to a 60% lower hazard of progression or death during the analysis period. Twelve-month PFS rates were 62.1% versus 28.4%.

These findings indicate that the higher response rate was accompanied by a significant improvement in disease control. However, median PFS not reached does not mean that progression will not occur, and longer follow-up is needed to characterize the durability of benefit.

Overall Survival and Depth of Response

Twelve-month overall survival (OS) was 87.9% with etentamig and 72.0% with SAT (HR, 0.48; 95% CI, 0.29–0.77). However, the prespecified OS efficacy boundary had not been crossed at the data cutoff. The survival results are therefore encouraging but should not be interpreted as a formally successful confirmatory OS finding.

Among patients achieving complete response or better, 89.1% reportedly achieved measurable residual disease (MRD) negativity at a threshold of 10⁻⁵. This suggests deep responses in that subgroup, but MRD negativity does not establish complete eradication of disease or guarantee durable remission.

 Safety Findings and Clinical Implications

Among patients receiving the single step-up dose, CRS occurred in 28.3%; all reported cases were Grade 1 or 2, with no Grade 3 or higher events. One Grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS) event was reported.

However, Grade 3/4 infections occurred in 27.7% of etentamig-treated patients versus 19.2% with SAT. Grade 5 infections were less frequent with etentamig, at 1.5% versus 3.1%. AbbVie also reported treatment-emergent adverse event-related discontinuations of 3.6% versus 14% in the BLA announcement. Its September topline release reported 9.6% for SAT, a discrepancy that requires clarification.

The monthly dosing schedule and low incidence of severe CRS may support administration across a wider range of care settings, although infection risk and monitoring requirements remain important considerations.

Regulatory Significance

The BLA submission brings etentamig a step closer to potential regulatory review, but the treatment remains investigational and has not been approved by the FDA. CERVINO’s results support further evaluation of etentamig as a potential option for heavily pretreated RRMM. The balance between improved response and PFS, infection risk, dosing convenience and longer-term outcomes will be important in assessing its eventual clinical role.

Reference

AbbVie Submits Biologics License Application (BLA) for Etentamig to U.S. FDA for Adults Living with Relapsed/Refractory Multiple Myeloma, AbbVie, 27 October 2026

Study Assessing Activity of Intravenous (IV) Etentamig Monotherapy Versus Standard Available Therapies in Adult Participants with Relapsed or Refractory Multiple Myeloma (CERVINO), ClinicalTrials.gov ID NCT06158841