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AbbVie’s monthly BCMAxCD3 bispecific clears Phase III hurdle

AbbVie’s monthly BCMAxCD3 bispecific clears Phase III hurdle

AbbVie (NYSE: ABBV) has reported that etentamig, its investigational BCMA × CD3 bispecific T-cell engager (TCE), met both dual primary endpoints in the Phase III CERVINO trial, delivering a 74% objective response rate (ORR) and a 60% reduction in the risk of disease progression or death versus investigator's choice of standard available therapies in triple-class exposed relapsed/refractory multiple myeloma (RRMM). The Independent Data Monitoring Committee recommended unblinding the study based on the magnitude of benefit observed at the first planned efficacy interim analysis.

The results put AbbVie on track for a regulatory submission by end of 2026, a timeline the company signaled earlier this year and reaffirmed at its Q2 earnings call in July, where management said a positive interim progression-free survival (PFS) analysis would trigger filings in the same year.

In 393 patients with a median of three prior lines of therapy, etentamig produced an ORR of 74.0% versus 45.7% for standard therapy (P<0.0001) and a PFS hazard ratio of 0.40 (95% CI, 0.29–0.54; P<0.0001), consistent across all pre-specified subgroups. Twelve-month overall survival was 87.9% versus 72.0% (HR 0.48; nominal P=0.0012), though the pre-specified efficacy boundary for OS was not crossed at this data cutoff. The drug was administered once every four weeks from initiation following a single step-up dose — a dosing schedule designed to reduce the cytokine release syndrome (CRS) burden that has constrained adoption of the approved bispecific antibodies in this class.

Among patients receiving the single step-up dose, any-grade CRS occurred in 28.3%, with 23.9% grade 1 and no grade 3 or higher events. Immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 0.9% of patients (grade 1 only). Grade 3/4 infections were higher with etentamig than standard therapy (27.7% vs. 19.2%), though fatal infections were lower (1.5% vs. 3.1%). Treatment discontinuations due to adverse events were 3.6% with etentamig versus 9.6% with standard therapy.

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Etentamig is engineered with a low-affinity CD3-binding domain to limit cytokine release, a bivalent high-avidity BCMA-binding domain, and a retained FcRn interaction that supports extended half-life and the monthly dosing schedule. AbbVie notes that clinical correlations of these structure-activity relationships have not been fully established.

The approved BCMA-directed bispecific antibodies — Janssen's Tecvayli (teclistamab), Pfizer's Elrexfio (elranatamab), and Regeneron's Lynozyfic (linvoseltamab) — are all administered weekly or biweekly, at least initially, and carry requirements for step-up dosing and CRS monitoring that have limited their use outside specialized centers. Etentamig also showed activity in patients with prior BCMA-targeted therapy exposure: Phase Ib data presented at ASCO 2026 showed a 64% ORR in patients who had received BCMA-directed CAR-T in the prior line.

Full data from CERVINO will be presented in a plenary session at the International Myeloma Society Annual Meeting on September 25, 2026, in Glasgow. AbbVie said it plans to discuss the results with global regulatory authorities to determine next steps. A Phase III combination study of etentamig with pomalidomide in second-line-plus patients, including those previously exposed to anti-CD38 antibodies or BCMA-directed therapies, is planned to begin by year-end.


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