Epcoritamab Plus R-CHOP Improves Progression-Free Survival Over R-CHOP Alone in Newly Diagnosed Patients With Diffuse Large B-Cell Lymphoma

Clinical Summary:

• Design/Population: The phase 3 EPCORE DLBCL-2 trial evaluated fixed-duration subcutaneous epcoritamab plus R-CHOP in newly diagnosed patients with diffuse large b-cell lymphoma and an International Prognostic Index (IPI) score of 2 to 5.
• Key Outcomes: Epcoritamab plus R-CHOP reduced the risk of disease progression or death by 51% in the primary analysis of patients with an IPI score of 3 to 5. A similar progression-free survival benefit was reported across the broader population with IPI scores of 2 to 5. 
• Clinical Relevance: These findings provide phase 3 evidence supporting the addition of epcoritamab to frontline R-CHOP for newly diagnosed patients with diffuse large b-cell lymphoma. The combination remains investigational, with detailed results and regulatory review still pending. 

Topline findings from the phase 3 EPCORE DLBCL-2 trial showed that adding epcoritamab to R-CHOP significantly improved progression-free survival (PFS) compared with R-CHOP alone in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL). 

In this multicenter, open-label trial, patients were randomized 2:1 to receive either 6 cycles of epcoritamab plus R-CHOP followed by 2 cycles of epcoritamab monotherapy or 6 cycles of R-CHOP followed by 2 cycles of rituximab. Eligible patients included those with DLBCL not otherwise specified, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, grade 3B follicular lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, and Epstein-Barr virus-positive DLBCL. Patients were required to have an International Prognostic Index (IPI) score ranging from 2 to 5.

The primary end point was PFS among patients with an IPI score of 3 to 5. Key secondary end points included PFS in the overall population of patients with an IPI score of 2 to 5 and safety. 

In the primary end point population, epcoritamab plus R-CHOP reduced the risk of disease progression or death by 51% compared with R-CHOP alone (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.35 to 0.69; P < .0001). 

The PFS benefit was also observed in the broader population of patients with IPI scores of 2 to 5. In this group, epcoritamab plus R-CHOP was associated with a 51% reduction in the risk of disease progression or death (HR, 0.49; 95% CI, 0.36 to 0.67; P < .0001).

No unexpected safety findings were identified in the topline announcement. The reported safety findings with epcoritamab plus R-CHOP were in line with what has previously been observed with the individual components of the regimen. 

Epcoritamab is a subcutaneously administered bispecific antibody designed to bind CD3 on T cells and CD20 on B cells, directing T-cell activity against CD20-expressing cells.

Epcoritamab plus R-CHOP remains investigational in this setting. Detailed findings are expected to be submitted for presentation at a future medical meeting, and Genmab and AbbVie plan to discuss the results with regulatory authorities. 

Source:

Genmab. Genmab and AbbVie announce epcoritamab in combination with R-CHOP demonstrates statistically significant improvement in progression-free survival in patients with newly diagnosed diffuse large b-cell lymphoma. Accessed on: October 6, 2026. https://ir.genmab.com/news-releases/news-release-details/genmab-and-abbvie-announce-epcoritamab-combination-r-chop/