Genmab A/S announced positive topline results from its Phase 3 EPCORE DLBCL-4 trial, evaluating a combination of epcoritamab (a T-cell engaging bispecific antibody) and lenalidomide in adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The trial, which compared the chemotherapy-free regimen against standard-of-care rituximab plus gemcitabine plus oxaliplatin (R-GemOx), successfully met its primary objective by demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS). This marks a crucial step for epcoritamab's expanded use beyond its initial accelerated FDA approval for third-line and later DLBCL. The company plans to engage global regulatory authorities following these results.

The combined therapy showed a substantial reduction in the risk of disease progression or death. Depending on regional censoring rules, the risk reduction was 60% (Hazard Ratio [HR] 0.40; 95% CI 0.30–0.55; p value < 0.0001) in the U.S. and 56% (HR 0.44; 95% CI 0.33–0.60; p value < 0.0001) outside the U.S. The safety profile of epcoritamab in combination with lenalidomide was consistent with the known profiles of the individual agents, suggesting no new major safety concerns. This chemotherapy-free, fixed-duration regimen offers a new potential option for patients who have received at least one prior line of treatment and failed or are ineligible for autologous stem cell transplantation.

This success follows an earlier Phase 3 trial (EPCORE DLBCL-1) where epcoritamab monotherapy improved PFS but did not reach statistical significance for overall survival. However, the positive outcome of EPCORE DLBCL-4, particularly in a second-line and beyond setting with an active-controlled design, provides compelling data for full regulatory approval. Analysts are optimistic about epcoritamab's potential to become a core therapy across B-cell malignancies, emphasizing the significance of this chemotherapy-free approach for a heavily pretreated patient population. Detailed data from the EPCORE DLBCL-4 trial will be presented at a future medical meeting and used for discussions with regulatory authorities globally.