AbbVie's Etentamig Meets Both Primary Endpoints in Phase 3 CERVINO Trial for Triple-Class Exposed Myeloma

AbbVie (NYSE: ABBV) reported positive topline results from the Phase 3 CERVINO trial of etentamig (ABBV-383), an investigational BCMA x CD3 bispecific T-cell engager, versus investigator’s choice of standard available therapies (SAT) in triple-class exposed relapsed/refractory multiple myeloma (RRMM). The study met both dual primary endpoints of objective response rate (ORR) and progression-free survival (PFS), and the independent data monitoring committee recommended unblinding the study.

The numbers

At the first planned efficacy interim analysis, CERVINO enrolled 393 patients who had received a median of three prior lines of therapy, with a median follow-up of 11.4 months:

• ORR: 74.0% for etentamig vs. 45.7% for SAT (P<0.0001)
• PFS: hazard ratio 0.40 (95% CI 0.29-0.54; P<0.0001), a 60% reduction in the risk of progression or death, consistent across all prespecified subgroups
• 12-month overall survival: 87.9% vs. 72.0% (HR 0.48; nominal P=0.0012) - but the prespecified efficacy boundary for OS was not crossed at this cutoff

The safety story

The profile AbbVie is leading with is safety and convenience. Etentamig uses a single step-up dose followed by monthly (Q4W) dosing from initiation. Cytokine release syndrome occurred in 28.3% of patients but was predominantly grade 1 (23.9%), with no grade 3 or higher events. Immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in one patient (0.9%, grade 1). Grade 5 (fatal) infections were 1.5% for etentamig versus 3.1% for SAT, though grade 3/4 infections ran higher for etentamig (27.7% vs. 19.2%), and discontinuations related to treatment-emergent adverse events were 3.6% versus 9.6%.

Why it matters

Etentamig is a second-generation BCMA bispecific built around a low-affinity CD3 binding domain (designed to cut CRS and infections), a high-avidity bivalent BCMA-binding domain, and retained FcRn binding that enables monthly dosing. That combination targets the adoption bottlenecks that have held back first-generation bispecifics like J&J’s TECVAYLI and TALVEY - namely step-up dosing schedules and the specialized monitoring infrastructure that limits access outside academic centers.

The efficacy is strong but not a clean win: OS favored etentamig numerically but did not cross its prespecified significance boundary, so the case for the drug rests on the safety and convenience profile rather than a demonstrated survival benefit. AbbVie said it plans to discuss the results with global regulators to determine next steps; full data, including depth of response and measurable residual disease negativity, land in a plenary session at the International Myeloma Society annual meeting on September 25.

For context on the crowded field etentamig is entering, see our earlier coverage of J&J’s TECVAYLI plus TALVEY combo, which cut progression risk by 89% in its own Phase 3 trial, and our breakdown of CAR-T versus bispecifics in multiple myeloma.

ABBV shares were little changed Thursday, last around $260 against a prior close of $261.72, reflecting a readout that is material to AbbVie’s oncology pipeline but small relative to its market capitalization.