Denmark-based Genmab and partner AbbVie reported that the Phase III EPCORE DLBCL-4 trial met its primary endpoint, moving Epkinly (epcoritamab) closer to expanding beyond its current accelerated approval for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more prior lines of therapy. The CD20×CD3 bispecific reduced the risk of disease progression or death by 60% versus rituximab plus gemcitabine and oxaliplatin (R-GemOx), potentially establishing a chemotherapy-free treatment option for patients who are ineligible for autologous stem cell transplantation (ASCT) or CAR-T cell therapy.
The positive Phase III result supports Genmab's effort to move epcoritamab into the second-line setting, where treatment options remain limited for patients unable to undergo ASCT or receive CAR-T therapy. If approved, the indication would represent a significant expansion beyond the drug's current use in later-line disease.
The EPCORE DLBCL-4 trial enrolled adults with relapsed or refractory large B-cell lymphoma, including DLBCL and other aggressive histological subtypes, who had failed or were ineligible for ASCT and could not receive CAR-T therapy. Epcoritamab plus lenalidomide achieved a hazard ratio of 0.40 (95% CI 0.30–0.55; p<0.0001), corresponding to a 60% reduction in the risk of disease progression or death versus R-GemOx. A parallel analysis using non-US censoring rules also met the primary endpoint, with a hazard ratio of 0.44 (95% CI 0.33–0.60; p<0.0001). The safety profile was consistent with the known profiles of the individual agents.
The data position epcoritamab more competitively in an evolving second-line DLBCL landscape. Roche's Columvi (glofitamab), the other approved CD20×CD3 bispecific antibody, is approved for patients who have received at least two prior lines of therapy, although its pivotal studies were conducted in the third-line or later setting, limiting direct comparisons. Incyte and MorphoSys's Monjuvi (tafasitamab), combined with lenalidomide, is approved for transplant-ineligible patients but remains under accelerated approval pending confirmatory data. Pfizer's Adcetris (brentuximab vedotin), in combination with lenalidomide and rituximab, received full US FDA approval in February 2025 for relapsed or refractory large B-cell lymphoma after one or more prior lines of therapy. Cross-trial comparisons remain limited by differences in patient populations and study designs.