Genmab and AbbVie announced on June 29 that epcoritamab, a CD3xCD20 bispecific antibody marketed as part of the companies’ EPCORE clinical program, met its primary endpoint in a Phase 3 trial evaluating the drug in combination with lenalidomide against physician’s choice of chemoimmunotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma. The trial showed a statistically significant improvement in progression-free survival for patients randomized to the epcoritamab-lenalidomide arm.

Diffuse large B-cell lymphoma is the most common form of non-Hodgkin lymphoma, and while frontline chemoimmunotherapy cures a majority of patients, those who relapse or prove refractory to initial treatment face a considerably worse prognosis, particularly if they are not candidates for stem cell transplant or CAR-T cell therapy. Epcoritamab works by simultaneously binding CD3 on T cells and CD20 on malignant B cells, physically bridging the two to trigger T-cell-mediated killing of the lymphoma cells without requiring the weeks-long manufacturing process associated with CAR-T products.

The trial randomized patients to receive either epcoritamab administered subcutaneously in combination with lenalidomide, an immunomodulatory agent already used across several B-cell malignancies, or investigator’s choice of standard chemoimmunotherapy regimens. Genmab said the magnitude of the progression-free survival benefit was clinically meaningful, and detailed results, including duration of response, overall survival trends and safety data, are expected to be presented at a forthcoming major hematology conference rather than in the topline release.

Epcoritamab already carries an accelerated approval in the United States for relapsed or refractory disease as a monotherapy following at least two prior lines of systemic therapy, granted on the strength of overall response rate data from an earlier single-arm trial. This new randomized dataset, evaluating the drug earlier and in combination rather than as a later-line monotherapy, is designed to support both a potential label expansion and conversion of the existing accelerated approval to full approval, a conversion the FDA has increasingly scrutinized across the bispecific antibody class in recent years.

Safety data from earlier epcoritamab studies have shown cytokine release syndrome as the most common serious adverse event, typically manageable with step-up dosing and premedication protocols that have become standard practice for CD3-engaging bispecifics. AbbVie and Genmab did not disclose a new safety signal in the topline announcement, though full toxicity data from the combination regimen, including how lenalidomide’s known cytopenia risk interacts with epcoritamab’s immune activation, will be closely watched by treating oncologists.

The result adds to a competitive field of bispecific antibodies targeting CD20 in B-cell lymphomas, including Roche’s mosunetuzumab and Regeneron’s odronextamab, all vying to move earlier into treatment sequencing as data matures. For Genmab, the outcome reinforces the commercial thesis behind its DuoBody platform, while for AbbVie it strengthens a hematology-oncology portfolio built substantially around the 2020 acquisition that brought the companies’ collaboration together.