Phase III EPCORE DLBCL-1 trial: Epcoritamab vs CIT in R/R LBCL

Results from the global, randomized, phase III EPCORE DLBCL-1 trial (NCT04628494), evaluating epcoritamab monotherapy vs investigator’s choice chemoimmunotherapy (CIT; rituximab + gemcitabine/oxaliplatin or bendamustine + rituximab) in 483 patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) ineligible for, or relapsed after, high-dose therapy with autologous hematopoietic stem cell transplantation (HDT-auto-HSCT), were presented by Christopher Fox at the European Hematology Association (EHA) 2026 Congress, June 11–14, 2026, Stockholm, SE. The primary endpoints included progression-free survival (PFS) by Lugano criteria and overall survival (OS).

Key data: Epcoritamab significantly improved PFS vs CIT (median, 3.5 vs 3.0 months; hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.60–0.92; p = 0.0059) and demonstrated a markedly longer median duration of response (DoR; 36.8 vs 5.6 months). OS was not significantly different (median, 11.3 vs 10.3 months; HR, 0.96; p = 0.7285), confounded by COVID-19 mortality and greater subsequent therapy use in the CIT arm; post hoc adjusted analysis yielded HR 0.76 (95% CI, 0.59–0.99). Overall response rate (ORR) was 51% vs 48% (p = 0.526), with complete response rate (CRR) 38% vs 26% (p = 0.0032). Safety was consistent with epcoritamab’s established profile.

Key learning: Epcoritamab monotherapy demonstrated a significant and clinically meaningful improvement in PFS, DoR, and CRR compared with investigator’s choice CIT in patients with R/R LBCL, supporting consideration of epcoritamab as a chemotherapy-free treatment option in this setting. Although the primary OS analysis was not statistically significant, its interpretation was limited by COVID-19 mortality and differential use of subsequent therapies.