ICML 2025 | Results from EPCORE NHL-2 trial of epcoritamab + R-CHOP for previously untreated DLBCL

During the 18th International Conference on Malignant Lymphomas (ICML), Jun 17–21, 2025, Lugano, CH, the Lymphoma Hub was pleased to speak with Joshua Brody from the Icahn School of Medicine at Mount Sinai, New York, US. We asked about the clinical significance of the long-term results from the EPCORE NHL-2 (NCT04663347) trial, which evaluated epcoritamab (epcor) in combination with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP) in patients with B-cell non-Hodgkin lymphoma. 

During this interview, Dr Joshua Brody discussed the latest data presented at the 18th ICML 2025 from the EPCORE NHL-2 study, with a focus on the cohort of patients with high-risk diffuse large B-cell lymphoma (DLBCL) treated with epcor + R-CHOP as frontline therapy. Brody highlighted the significance of durable remission in this difficult-to-treat population, provided an overview of the top-line data from the trial, and discussed upcoming developments, including the phase III randomized EPCORE DLBCL-2 (NCT05578976) trial, which is currently underway and will further evaluate the efficacy and safety of adding epcor to standard R-CHOP in this high-risk patient population.

Key learnings

• Epcor is a CD20×CD3-directed bispecific antibody therapy.
• This analysis of patients with high-risk DLBCL included patients with International Prognostic Index ≥3.
• At a median follow-up of 24 months, 83% of patients treated with epcor + R-CHOP remained in remission.¹
• The 2-year progression-free survival rate in this cohort was 82%.¹
• Cytokine release syndrome (CRS) was observed and attributed to epcor; however, the majority of cases were Grade 1 or 2, with Grade 3 CRS occurring in 4% of patients.¹
• The phase III randomized EPCORE DLBCL-2 trial evaluating this regimen is currently underway, with efficacy data expected within the next year.
• These findings suggest that the addition of epcor to R-CHOP could represent a potential advancement in frontline treatment for high-risk DLBCL, pending validation in larger randomized studies.