Genmab and AbbVie announced that epcoritamab, a subcutaneously administered CD3xCD20 bispecific antibody, met its primary endpoint in a Phase 3 trial evaluating the drug in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), the most common form of non-Hodgkin lymphoma in adults. The companies did not disclose full numerical results, saying detailed data will be presented at an upcoming hematology congress, but confirmed the trial crossed its statistical threshold for progression-free survival compared with standard-of-care chemoimmunotherapy.

Epcoritamab works by simultaneously binding CD3 on T cells and CD20 on malignant B cells, physically bridging the two and triggering the T cell to destroy the tumor cell without requiring prior genetic engineering, the approach used in CAR-T therapies. The drug already carries accelerated approval in the U.S. for DLBCL patients who have progressed after at least two prior lines of systemic therapy, granted on the strength of the EPCORE NHL-1 trial’s response rate data. This new Phase 3 result is expected to support a move toward full approval and, longer term, use earlier in the treatment sequence.

DLBCL affects roughly 25,000 to 30,000 patients annually in the U.S. alone, and while frontline R-CHOP chemotherapy cures a majority of patients, close to forty percent relapse or prove refractory to initial treatment. Options for that population have expanded rapidly over the past five years with the arrival of CAR-T therapies from Gilead’s Kite and Novartis, alongside earlier bispecifics, but bispecific antibodies carry the practical advantage of being available off the shelf, without the manufacturing lag or apheresis logistics that CAR-T requires. That distinction has become central to how oncologists sequence therapy, particularly for patients whose disease is progressing quickly enough that a four to six week CAR-T manufacturing window is not tenable.

Genmab, based in Copenhagen, discovered epcoritamab and partnered with AbbVie in 2020 in a deal that included upfront and milestone payments exceeding $3.5 billion. The companies have run a broad development program spanning follicular lymphoma, chronic lymphocytic leukemia and now earlier lines of DLBCL treatment, betting that the subcutaneous formulation, which reduces infusion-related reactions relative to intravenous bispecifics, gives epcoritamab an edge as the class matures.

Cytokine release syndrome remains the primary safety concern with CD3-engaging bispecifics, and the companies said the safety profile in this trial was consistent with prior studies, with step-up dosing during the first treatment cycle used to mitigate severe reactions. Regulatory filings based on the new data are expected within the year. If successful, epcoritamab would become one of the first bispecific antibodies to secure a frontline or near-frontline indication in aggressive lymphoma, a shift that would reshape treatment algorithms across academic and community oncology settings alike.